Method and apparatus for control of non-invasive parameter measurements

ABSTRACT

Improved methods and apparatus for non-invasively assessing one or more parameters associated with fluidic systems such as the circulatory system of a living organism. In a first aspect, an improved method of continuously measuring pressure from a compressible vessel is disclosed, wherein a substantially optimal level of compression for the vessel is achieved and maintained using perturbations (e.g., modulation) of the compression level of the vessel. In one exemplary embodiment, the modulation is conducted according to a pseudo-random binary sequence (PBRS). In a second aspect, an improved apparatus for determining the blood pressure of a living subject is disclosed, the apparatus generally comprising a pressure sensor and associated processor with a computer program defining a plurality of operating states related to the sensed pressure data. Methods for pressure waveform correction and reacquisition, as well as treatment using the present invention, are also disclosed.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates generally to methods and apparatus for monitoringparameters associated with circulating fluid systems, and specificallyin one aspect to the non-invasive monitoring of arterial blood pressurein a living subject.

2. Description of Related Technology

The accurate, continuous, non-invasive measurement of blood pressure haslong been sought by medical science. The availability of suchmeasurement techniques would allow the caregiver to continuously monitora subject's blood pressure accurately and in repeatable fashion withoutthe use of invasive arterial catheters (commonly known as “A-lines”) inany number of settings including, for example, surgical operating roomswhere continuous, accurate indications of true blood pressure are oftenessential.

Several well known techniques have heretofore been used tonon-invasively monitor a subject's arterial blood pressure waveform,namely, auscultation, oscillometry, and tonometry. Both the auscultationand oscillometry techniques use a standard inflatable arm cuff thatoccludes the subject's peripheral (predominately brachial) artery. Theauscultatory technique determines the subject's systolic and diastolicpressures by monitoring certain Korotkoff sounds that occur as the cuffis slowly deflated. The oscillometric technique, on the other hand,determines these pressures, as well as the subject's mean pressure, bymeasuring actual pressure changes that occur in the cuff as the cuff isdeflated. Both techniques determine pressure values only intermittently,because of the need to alternately inflate and deflate the cuff, andthey cannot replicate the subject's actual blood pressure waveform.Thus, continuous, beat-to-beat blood pressure monitoring cannot beachieved using these techniques.

Occlusive cuff instruments of the kind described briefly above havegenerally been somewhat effective in sensing long-term trends in asubject's blood pressure. However, such instruments generally have beenineffective in sensing short-term blood pressure variations, which areof critical importance in many medical applications, including surgery.

The technique of arterial tonometry is also well known in the medicalarts. According to the theory of arterial tonometry, the pressure in asuperficial artery with sufficient bony support, such as the radialartery, may be accurately recorded during an applanation sweep when thetransmural pressure equals zero. The term “applanation” refers to theprocess of varying the pressure applied to the artery. An applanationsweep refers to a time period during which pressure over the artery isvaried from overcompression to undercompression or vice versa. At theonset of a decreasing applanation sweep, the artery is overcompressedinto a “dog bone” shape, so that pressure pulses are not recorded. Atthe end of the sweep, the artery is undercompressed, so that minimumamplitude pressure pulses are recorded. Within the sweep, it is assumedthat an applanation occurs during which the arterial wall tension isparallel to the tonometer surface. Here, the arterial pressure isperpendicular to the surface and is the only stress detected by thetonometer sensor. At this pressure, it is assumed that the maximumpeak-to-peak amplitude (the “maximum pulsatile”) pressure obtainedcorresponds to zero transmural pressure. Note that other measuresanalogous to maximum pulsatile pressure, including maximum rate ofchange in pressure (i.e., maximum dP/dT) can also be implemented.

One prior art device for implementing the tonometry technique includes arigid array of miniature pressure transducers that is applied againstthe tissue overlying a peripheral artery, e.g., the radial artery. Thetransducers each directly sense the mechanical forces in the underlyingsubject tissue, and each is sized to cover only a fraction of theunderlying artery. The array is urged against the tissue, to applanatethe underlying artery and thereby cause beat-to-beat pressure variationswithin the artery to be coupled through the tissue to at least some ofthe transducers. An array of different transducers is used to ensurethat at least one transducer is always over the artery, regardless ofarray position on the subject. This type of tonometer, however, issubject to several drawbacks. First, the array of discrete transducersgenerally is not anatomically compatible with the continuous contours ofthe subject's tissue overlying the artery being sensed. This can resultin inaccuracies in the resulting transducer signals. In addition, insome cases, this incompatibility can cause tissue injury and nervedamage and can restrict blood flow to distal tissue.

Other prior art techniques have sought to more accurately place a singletonometric sensor laterally above the artery, thereby more completelycoupling the sensor to the pressure variations within the artery.However, such systems may place the sensor at a location where it isgeometrically “centered” but not optimally positioned for signalcoupling, and further typically require comparatively frequentre-calibration or repositioning due to movement of the subject duringmeasurement.

Tonometry systems are also commonly quite sensitive to the orientationof the pressure transducer on the subject being monitored. Specifically,such systems show a degradation in accuracy when the angularrelationship between the transducer and the artery is varied from an“optimal” incidence angle. This is an important consideration, since notwo measurements are likely to have the device placed or maintained atprecisely the same angle with respect to the artery. Many of theforegoing approaches similarly suffer from not being able to maintain aconstant angular relationship with the artery regardless of lateralposition, due in many cases to positioning mechanisms which are notadapted to account for the anatomic features of the subject, such ascurvature of the wrist surface.

Furthermore, compliance in various apparatus components (e.g., the strapand actuator assembly) and the lack of soft padding surrounding thesensor which minimizes edge effects may adversely impact the accuracy oftonometric systems to a significant extent.

One very significant limitation of prior art tonometry approachesrelates to the magnitude and location of the applied applanationpressure during varying conditions of patient motion, position, meanpressure changes, respiration, etc. Specifically, even when the optimumlevel of arterial compression at the optimal coupling location isinitially achieved, there are commonly real-world or clinical factorsbeyond reasonable control that can introduce significant error into themeasurement process, especially over extended periods of time. Forexample, the subject being monitored may voluntarily or involuntarilymove, thereby altering (for at least a period of time) the physicalrelationship between the tonometric sensor and the subject'stissue/blood vessel. Similarly, bumping or jarring of the subject or thetonometric measurement apparatus can easily occur, thereby againaltering the physical relationship between the sensor and subject. Thesimple effect of gravity can, under certain circumstances, cause therelative positions of the sensor and subject blood vessel to alter withtime as well.

Furthermore, physiologic responses of the subject (including, forexample, relaxation of the walls of the blood vessel due to anesthesiaor pharmacological agents) can produce the need for changes in theapplanation level (and sometimes even the lateral/proximal position ofthe sensor) in order to maintain optimal sensor coupling. Additionally,due to the compliance of surrounding tissue and possibly measurementsystem, the applanation level often needs to adjust with changes in meanarterial pressure.

Several approaches have heretofore been disclosed in attempts to addressthe foregoing limitations. In one prior art approach, an occlusive cuffis used to provide a basis for periodic calibration; if the measuredpressure changes a “significant” amount or a determined time haselapsed, then the system performs a cuff calibration to assist inresetting the applanation position. Reliable pressure data is notdisplayed or otherwise available during these calibration periods. Seefor example U.S. Pat. No. 5,261,414 to Aung, et al issued Nov. 16, 1993and entitled “Blood-Pressure Monitor Apparatus,” assigned to ColinCorporation (hereinafter “Aung”). See also U.S. Pat. No. 6,322,516issued Nov. 27, 2001 and entitled “Blood-Pressure Monitor Apparatus,”also assigned to Colin Corporation, wherein an occlusive cuff is used asthe basis for calibration of a plurality of light sensors.

In another prior art approach, a pressure cuff or a pelotte equippedwith a plethysmographic gauge, such as an impedance or a photo-electricdevice, is used to drive a servo control loop. See, e.g., U.S. Pat. No.4,869,261 to Penaz issued Sep. 26, 1989 and entitled “Automaticnoninvasive blood pressure monitor,” assigned to University J. E.Purkyne v Brne (hereinafter “Penaz”). In this device, the sensor isconnected through at least one amplifier and a phase corrector to anelectro-pressure transducer. All these components constitute the closedloop of a servo control system which (at least ostensibly) continuouslychanges the pressure in the cuff and attempts to maintain the volume ofthe artery at a value corresponding to zero tension across the arterialwall. The servo control system loop further includes a pressurevibration generator, the frequency of vibration being higher than thatof the highest harmonic component of blood pressure wave. A correctioncircuit is also provided, the input of which is connected to theplethysmographic sensor and output of which is provided to correct thesetpoint of the servo control system. The Penaz system therefore ineffect constantly “servos” (within a cardiac cycle) to a fixed lightsignal level received from the sensor. Unlike the Colin systemsdescribed above, the system continuously displays pressure to theoperator. However, the operation of the plethysmographic sensor of Penazlimited the application of this device to a peripheral section of a limb(preferably a finger) where the peripheral pressure, especially underconditions of compromised peripheral circulation, may not accuratelyreflect aortic or brachial artery pressure. This presents a potentiallysignificant cause of error.

Yet another prior art approach uses a series of varying pressure“sweeps” performed successively to attempt to identify the actualintra-arterial blood pressure. The applanation pressure applied duringeach of these sweeps is generally varied from a level of arterialundercompression to overcompression (or vice-versa), and the systemanalyzes the data obtained during each sweep to identify, e.g., thelargest pressure waveform amplitude. See, e.g., U.S. Pat. No. 5,797,850to Archibald, et al issued Aug. 25, 1998 and entitled “Method andapparatus for calculating blood pressure of an artery,” assigned toMedwave, Inc. (hereinafter “Archibald”). The system of Archibald is nottruly continuous, however, since the sweeps each require a finite periodof time to complete and analyze. In practice the sweeps are repeatedwith minimal delay, one after another, throughout the operation of thedevice. During applanation mechanism resetting and subsequent sweepoperations, the system is effectively “dead” to new data as it analyzesand displays the data obtained during a previous sweep period. This isclearly disadvantageous from the standpoint that significant portions ofdata are effectively lost, and the operator receives what amounts toonly periodic indications of the subject's blood pressure (i.e., one newpressure beat display every 15–40 seconds).

Lastly, the techniques for non-invasive pressure measurement disclosedby the Assignee of the present invention in U.S. Pat. Nos. 6,228,034,6,176,831, 5,964,711, and 5,848,970, each entitled “Apparatus and methodfor non-invasively monitoring a subject's arterial blood pressure” andincorporated herein by reference in their entirety, include modulationof applanation level at, inter alia, frequencies higher than the heartrate (e.g., sinusoidal perturbation at 25 Hz). While the foregoingmethods are effective, Assignee has determined over time that it isdesirable at certain circumstances to control the applanation levelaccording to other modulation schemes and/or frequencies, and/or whichare not regular or deterministic in nature. Furthermore, certainmodulation schemes (e.g., intra-beat modulation) can place significantdemands on the applanation hardware, since more rapid (and oftenprecise) variations in applanation level must occur. Accordingly, themore capable hardware required in such applications ultimately raisesthe cost of the parent device in which it is used.

Based on the foregoing, there is needed an improved methodology andapparatus for accurately and continuously controlling the non-invasivemeasurement of parameters such as pressure. Such improved methodologyand apparatus would ideally allow for, inter alia, continuousmeasurement (tonometrically or otherwise) of one or more hemodynamicparameters, the measured values of such parameters being reflective oftrue intra-arterial parameters, while also providing robustness andrepeatability under varying environmental conditions including motionartifact and other noise. Such method and apparatus would also be easilyutilized by both trained medical personnel and untrained individuals,thereby allowing subjects to accurately and reliably conductself-monitoring if desired.

SUMMARY OF THE INVENTION

The present invention satisfies the aforementioned needs by improvedmethods and apparatus for non-invasively and continuously controllingthe measurement of parameters in a fluidic system, including arterialblood pressure within a living subject.

In a first aspect of the invention, an improved method of measuringhemodynamic data from a compressible vessel is disclosed. In oneembodiment, the method comprises: disposing a pressure sensor inproximity to the vessel; identifying a substantially optimal level ofcompression for the vessel; achieving the substantially optimal level ofcompression; measuring pressure data from the vessel using the sensor;identifying non-optimal levels of compression; and adjusting applanationto maintain or reacquire the optimal level of compression. The sensor isapplied tonometrically, and the method of maintaining optimal level ofcompression comprises at least periodically perturbing the level ofcompression of the vessel during the act of measuring to produce anobservable effect on the measured pressure data; and adjusting the levelof compression based at least in part on the effect. In one exemplaryembodiment, the vessel comprises a blood vessel, and the appliedperturbations comprises pseudo-random binary sequences which are used tomodulate the level of compression applied to the vessel over time.Effects on the sensed pressure are correlated to the modulation, andnecessary corrections applied thereto.

In a second aspect of the invention, an improved apparatus fordetermining the blood pressure of a living subject is disclosed. In oneembodiment, the apparatus comprises: a tonometric pressure sensor deviceadapted for sensing the pressure at the skin surface of a living subjectand generating pressure data relating thereto; and a processor adaptedto run a computer program thereon, the computer program defining aplurality of operating states, the use of each of the operating statesby the apparatus in determining blood pressure being related at least inpart to the pressure data. In one exemplary embodiment, the computerprogram comprises three (3) distinct sub-processes relating to transientdetection and compensation, servoing (or slower-rate changes tocoupling), and reacquisition after loss of coupling, respectively. Thefirst process in this exemplary embodiment employs four (4) distinct butrelated states which govern applanation and lateral/proximalpositioning.

In a third aspect of the invention, a method of transient eventcompensation is disclosed. In one embodiment, the compensation is usedduring hemodynamic parameter measurement from a compressible bloodvessel, and the method comprises: establishing an initial substantiallyoptimal level of compression of the blood vessel for at least a firstepoch; measuring pressure data from the blood vessel using a sensor;detecting the occurrence of a transient event by analyzing changes inthe pressure data, the transient event altering the mechanical couplingbetween the blood vessel and sensor; initiating a pressure sweep toidentify a second substantially optimal level of compression based onthe altered coupling; and establishing the second substantially optimallevel of compression of the blood vessel for at least a second epoch.

In a fourth aspect of the invention, a method of operating a continuousnon-invasive blood pressure measurement system is disclosed. In oneembodiment, the system is adapted for use on the radial artery of aliving subject and having a tonometric pressure sensor in contact withthe tissue overlying the artery, and the method comprises: operating thesystem in a non-transient mode, wherein blood pressure data is obtainedusing the sensor; detecting at least one transient event using the bloodpressure data; and operating the system in a transient recovery modesubsequent to the detection of the event.

In a fifth aspect of the invention, a method of operating a non-invasivehemodynamic measurement system is disclosed. In one embodiment, themethod comprises: operating the system in a first mode, whereinhemodynamic data is obtained; detecting at least one transient eventwithin the hemodynamic data; and (i) operating the system in a secondmode subsequent to the detection of the event if the event does not havea first characteristic; and (ii) operating the system in a third modesubsequent to the detection if the event has the first characteristic;wherein the first characteristic comprises parameters indicating thatthe event is not (a) physiologic in origin, and (b) of sufficientmagnitude that recovery from the event in the second mode would exceed afirst criterion.

In a sixth aspect of the invention, a method of operating a non-invasiveblood pressure measurement apparatus is disclosed. In one embodiment,the method comprises: collecting pressure data in a non-transient mode;detecting the occurrence of at least one transient event based at leastin part on the data; operating the apparatus in a transient recoverymode subsequent to the detection of the event; and operating in a secondnon-transient mode when non-transient induced changes occur, thenon-transient changes being detected at least in part by modulating acompression level of a blood vessel from which the data is obtained.

In a seventh aspect of the invention, a method of operating anon-invasive hemodynamic measurement system is disclosed. In oneembodiment, the method comprises: operating the system in a servo mode,wherein hemodynamic data is obtained; detecting at least one transientevent within the hemodynamic data; and operating the system in atransient recovery mode subsequent to the detection of the event, thetransient recovery mode being adapted to promptly return the system tothe servo mode.

In an eighth aspect of the invention, non-invasive blood pressuremeasurement apparatus is disclosed. In one embodiment, the apparatus isadapted to operate according to the method comprising: operating theapparatus in a non-transient mode, wherein pressure data is obtained;detecting at least one transient event from at least the data; andoperating the apparatus in a transient recovery mode subsequent to thedetection of the event; wherein the transient recovery mode comprises amode adapted to compensate for the at least one transient event, andpromptly return the system to the non-transient mode.

These and other features of the invention will become apparent from thefollowing description of the invention, taken in conjunction with theaccompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a state diagram illustrating the relationship of the fourstates associated with a first exemplary embodiment of the first processof the present invention.

FIG. 1 a is logical flow diagram illustrating the operation of theexemplary embodiment of the first process of FIG. 1.

FIG. 2 is logical flow diagram illustrating the operation of oneexemplary embodiment of the second process (e.g., servoing ormaintaining optimal applanation level) according to the invention.

FIG. 2 a is a graph of pulse pressure versus diastolic pressure for anexemplary patient.

FIG. 2 b is a graph of tonometric pressure versus time for the optimalarterial compression (applanation) of the patient of FIG. 2 a.

FIG. 2 c is a graph of tonometric pressure versus time for both optimaland non-optimal applanation level applied to the patient of FIG. 2 a.

FIG. 2 d is a graph of an exemplary embodiment of the modulation schemeaccording to the present invention, illustrating the PRBS modulationvalue versus applanation motor step number.

FIG. 2 e is a graph of the tonometric pressure obtained from the patientof FIG. 2 a with and without PRBS modulation applied to non-optimalapplanation, illustrating the effects of PRBS modulation.

FIG. 2 f is a graph of the corrected or restored tonometric pressurewaveform after application of PRBS modulation to the non-optimalapplanation profile.

FIG. 2 g is a graph of an exemplary embodiment of the PRBS modulation ofthe invention (PRBS length=7), illustrating the correlation betweenmodulation and corrected pulse pressure.

FIG. 2 h is a graph of pressure versus beat number illustrating thecorrelation between the weighted zero mean values for exemplary pulsepressure and diastolic pressure, and PRBS modulation.

FIG. 2 i is a graph of pressure versus phase delay for pulse pressure,diastolic pressure, and PRBS modulation according to one embodiment ofthe invention.

FIG. 3 is a logical flow diagram illustrating one exemplary embodimentof the method of determining the optimal initial modulation according tothe present invention.

FIGS. 3 a and 3 b are graphs illustrating various aspects of thecalculations supporting the methodology of FIG. 3.

FIG. 4 is logical flow diagram illustrating the operation of oneexemplary embodiment of the third process (e.g., reacquisition)according to the invention.

FIG. 4 a is a graphical illustration of an exemplary embodiment of thefourth (“sweep”) state entry criteria associated with the third processof the invention.

FIG. 5 is a block diagram of one exemplary embodiment of the apparatusfor measuring hemodynamic parameters within the blood vessel of a livingsubject according to the invention.

FIG. 6 is a logical flow diagram illustrating one exemplary embodimentof the method of providing treatment to a subject using theaforementioned methods.

DETAILED DESCRIPTION OF THE INVENTION

Reference is now made to the drawings wherein like numerals refer tolike parts throughout.

It is noted that while the invention is described herein primarily interms of a method and apparatus for the control of non-invasivemeasurements of hemodynamic parameters such as blood pressure obtainedvia the radial artery (i.e., wrist) of a human subject, the inventionmay also be readily embodied or adapted to monitor such parameters atother blood vessels and locations on the human body, as well asmonitoring these parameters on other warm-blooded species. Similarly,the techniques of the present invention can be applied to other similarfluidic systems which have similar properties to those of thecirculatory system of a living being. All such adaptations and alternateembodiments are readily implemented by those of ordinary skill in therelevant arts, and are considered to fall within the scope of the claimsappended hereto.

As used herein, the term “hemodynamic parameter” is meant to includeparameters associated with the circulatory system of the subject,including for example pressure (e.g., diastolic, systolic, pulse, ormean pressure), derivatives or combinations thereof, arterial flow,arterial wall diameter (and its derivatives), cross sectional area ofthe artery, and arterial compliance.

Additionally, it is noted that the terms “tonometric,” “tonometer,” and“tonometery” as used herein are intended to broadly refer tonon-invasive surface measurement of one or more hemodynamic parameters,such as by placing a sensor in communication with the surface of theskin, although contact with the skin need not be direct, and can beindirect (e.g., such as through a coupling medium or other interface).

The terms “applanate” and “applanation” as used herein refer to thecompression (relative to a state of non-compression) of tissue, bloodvessel(s), and other structures such as tendon or muscle of thesubject's physiology. Similarly, an applanation “sweep” refers to one ormore periods of time during which the applanation level is varied(either increasingly, decreasingly, or any combination thereof).Although generally used in the context of linear (constant velocity)position variations, the term “applanation” as used herein mayconceivably take on any variety of other forms, including withoutlimitation (i) a continuous non-linear (e.g., logarithmic) increasing ordecreasing compression over time; (ii) a non-continuous or piece-wisecontinuous linear or non-linear compression; (iii) alternatingcompression and relaxation; (iv) sinusoidal or triangular wavesfunctions; (v) random motion (such as a “random walk”; or (vi) adeterministic profile. All such forms are considered to be encompassedby the term.

As used herein, the term “epoch” refers to any increment of time,ranging in duration from the smallest measurable fraction of a second tomore than one second.

As used herein, the terms “spatial” and “position”, although describedin terms of a substantially Cartesian coordinate system havingapplanation (i.e., Z-axis), lateral (X-axis) and (Proximal refers tocloser to the heart) longitudinal or (proximal-distal) (Y-axis)components, shall refer to any spatial coordinate system including,without limitation, cylindrical, spherical, and polar. Such use ofalternate coordinate systems may clearly be independent of anyparticular hardware configuration or geometry (e.g., by performingsimple mathematical translations between a Cartesian-based apparatus andthe non-Cartesian coordinate system), or alternatively make advantageoususe of such geometries. The present invention is therefore in no waylimited to certain coordinate systems of apparatus configurations. Asone example, it will be recognized that the methods and apparatus of thepresent invention may be embodied using a cylindrical coordinate systemmodeled around the radial artery, such that a particular point in spacefor the tonometric sensor(s) can be specified by the Z, r, and θparameters. This approach may have advantages since the forearm/wristarea of the human being very roughly comprises a cylindrical form.

Lastly, the term “digital processor” is meant to include any integratedcircuit or other electronic device (or collection of devices) capable ofperforming an operation on at least one instruction including, withoutlimitation, reduced instruction set core (RISC) processors such as thosemanufactured by ARM Limited of Cambridge, UK, CISC microprocessors,microcontroller units (MCUs), CISC-based central processing units(CPUs), and digital signal processors (DSPs). The hardware of suchdevices may be integrated onto a single substrate (e.g., silicon “die”),or distributed among two or more substrates. Furthermore, variousfunctional aspects of the processor may be implemented solely assoftware or firmware associated with the processor.

Overview

In one fundamental aspect, the present invention comprises methods andapparatus for controlling an applanation or other positioning mechanismused in non-invasive hemodynamic parameter measurements in order to,inter alia, maintain optimal coupling between a parameter sensor and theblood vessel of interest. Techniques for determining the optimalapplanation level, position, and coupling are described in detail in,e.g., co-pending U.S. patent application Ser. No. 10/072,508 entitled“Method And Apparatus For Non-Invasively Measuring HemodynamicParameters Using Parametrics” filed Feb. 5, 2002, which is assigned tothe Assignee hereof and incorporated by reference herein in itsentirety.

While the techniques described in the aforementioned co-pending patentapplication have been determined by Assignee to be highly effective,their robustness and utility in practical (e.g., clinical) settings isenhanced through the addition of one or more of the various aspects ofthe present invention. Such additional robustness is highly desirable,since it effectively removes many operational restrictions on aclinician, caregiver, or user (hereinafter “operator”) when measuringhemodynamic parameters such as blood pressure. Specifically, theoperator is substantially relieved of having to monitor the signalderived from the measurement apparatus to detect anomalies, motionartifact, and under certain circumstances will even identify to theoperator when error conditions which cannot be corrected have in factoccurred.

After the applanation and lateral (and proximal, if desired) positionsthat provide the optimal mechanical coupling between the system sensorand the underlying blood vessel have been determined, the invention ofthe present disclosure is used to control and adjust the level ofapplanation and/or the lateral/proximal positions to maintain theoptimal coupling under potentially adverse environmental conditions suchas might be encountered in the average clinical setting. Due to thenature of the clinical setting and all of its variables, not everyenvironmental condition or influence can always be compensated for, andhence the present invention has as another function the ability toidentify conditions where changes in mechanical coupling have impactedthe accuracy or reliability of hemodynamic measurements in a meaningfulmanner.

Three separate but substantially interactive processes are used in thepresent invention to provide the aforementioned control andidentification functionalities: (i) a first process adapted to identifysudden changes in the mechanical coupling, as indicated for example bychanges in the measured parameter (such as tonometrically measuredpressure or pressure velocity) that exceed expected norms, and reacquireeither/both the optimal applanation level or lateral/proximal positionswhere appropriate; (ii) a second (non-transient) process or mode adaptedto continuously identify time varying changes in compression coupling,and controllably adjust the applanation position accordingly(“servoing”); and (iii) a third process adapted to operate interactivelywith the first state and provide warning and protection against loss ofoptimal coupling in one or more domains, as well as performing a newdetermination(s) of optimal position in an optimized fashion. The firstand third processes are each examples of transient recovery modes of theinvention.

The techniques and apparatus of the present invention may be used with asingle sensor (or array of sensors) as described in detail herein andthe aforementioned and incorporated co-pending application, or inconjunction with literally any type of other apparatus adapted forhemodynamic parameter measurement, including for example the devicesdescribed in co-pending U.S. patent application Ser. Nos. 09/815,982entitled “Method and Apparatus for the Noninvasive Assessment ofHemodynamic Parameters Including Blood Vessel Location” filed Mar. 22,2001, and 09/815,080 entitled “Method and Apparatus for AssessingHemodynamic Parameters within the Circulatory System of a LivingSubject” also filed Mar. 22, 2001, both of which are assigned to theassignee hereof and incorporated herein by reference in their entirety.For example, ultrasound measurements of blood pressure via blood flowkinetic energy or velocity can be used as a confirmatory technique for afundamentally tonometric pressure-based approach. As another example,lateral positioning based on analysis of the acoustic signals relatingto vessel wall detection may be used in addition to (or in place of) thepressure-based techniques described in the originally cited co-pendingpatent application. Hence, the various aspects of the present inventionare advantageously compatible with a number of different hemodynamicassessment techniques. It will also be recognized that the techniquesand apparatus described herein are in no way limited to tonometricapplications; rather, these features may be implemented even inocclusive cuff or pellot-based systems.

Since signals under measurement (e.g. pressure) are time variant,iteration and optimization are substantially used by the methodology ofthe present invention to account for this variation. Specifically, thepressure signal associated with a blood vessel is time variant over theshort period of the cardiac cycle, over the longer period of therespiratory cycle, and potentially over the even longer or shorterperiod of hemodynamic changes resulting from varying drug concentrationsand volume changes. Accordingly, the three processes referenced aboveutilize the aforementioned applanation and lateral/proximal positioningmechanisms to continually find and maintain the optimal position andlevel of applanation, thereby maintaining an environment conducive foraccurate, continuous, and non-invasive parametric measurement. In thosevery limited circumstances where such optimal position and level cannotbe reasonably or reliably maintained (such as an abrupt and jarringdislocation of the apparatus from the subject's anatomy), the presentinvention identifies such conditions accordingly, and optionally alertsthe operator or provides other notification.

Table 1 below summarizes the functionality and features of one exemplaryembodiment of the invention incorporating the three aforementionedprocesses.

TABLE 1 Feature First Process Second Process Third Process DetectionTime >5 Hz All Frequencies > Seconds Frequency of Changes RecoveryMethod Applanation Continuous Applanation Sweep Adjustment Sweep Time toRecover 10–20 seconds 20–120 seconds 10–20 seconds (Largely (Correlatedto (Largely Uncorrelated to Magnitude of Uncorrelated to Magnitude oferror) Magnitude of error) error) Lateral/Proximal Possible No No SearchPressure Display No: Recovery Yes No: Recovery Continuous Sweeps SweepsDescription of First Process

Referring now to FIG. 1–1 a, a first exemplary embodiment of the methodof identifying sudden changes in the mechanical coupling andreacquisition of either/both the optimal applanation level orlateral/proximal positions according to the invention is described indetail. A detailed discussion of the electronic and signal processingapparatus used to support the operation of the processes describedherein is provided with respect to FIG. 5 below. It will be appreciatedthat while portions of the following discussion are cast in terms ofapplanation (and lateral/proximal positioning) motors of thestepper-type, the techniques of the present invention may be utilized inconjunction with other types of applanation and positioning apparatus,and accordingly are in no way limited to the specific embodiments ofapparatus described herein.

It will also be recognized that while the first process is describedsubsequently herein with respect to a tonometric pressure transducer,the methodology of the invention can be applied more generally to othersignal domains. For example, sudden changes in the mechanical couplingof an ultrasonic transducer to a subject's tissue can be identifiedusing, inter alia, parameters which exceed physiological norms asindicia thereof or measureable distortion in the measurement process.Sudden changes in mechanical coupling will alter the measurement of manyparameters, both physiological in nature and otherwise.

Furthermore, it will be appreciated that while described in the contextof the aforementioned apparatus (i.e., a tonometric pressure sensorwhich also acts to provide varying levels of compression of theunderlying tissue and blood vessel(s)), the methodology of the presentinvention may be practiced using apparatus having separate componentswhich provide these functions. For example, the control of the pressuresensor may be partly or completely decoupled from the applanationcontrol system, such that the level of applanation can be variedindependently from the coupling of the active surface(s) of the sensor.

The first process of the present embodiment continuously checks for(sudden) changes in the mechanical coupling between a tonometricpressure sensor and the underlying vessel/tissue. Sudden changes inmechanical coupling can be identified by corresponding sudden changes intonometrically derived pressure P_(T) (first or second derivative ofpressure) that exceed physiologic norms. A velocity parameter, V_(p)[k],is calculated as in Eqn. 1:P _(T) [k]−P _(T) [k−3]  (Eqn. 1)where k represents the current sample, k-3 represents three samples inthe past where the sample rate is 160 Hz. Tonometrically measuredacceleration, Ap[k], is calculated as in Eqn. 2:V _(p[k]−V) _(p[k)−1]=P _(T [k]+P) _(T [k)4]−(P _(T [k)−1]+P _(T [k)−3])  (Eqn. 2)For each sample the pressure, velocity and acceleration are comparedwith fixed (or deterministic) thresholds. If any one of these parametersexceeds their respective thresholds, then a process “event” istriggered. Note that the pressure, velocity, and acceleration aretypically greater during the systolic pressure upstroke than during thediastolic pressure downstroke, hence the thresholds of the presentembodiment are set accordingly, providing effectively a “buffer” betweenphysiologic norms and process event triggers. This buffer enhancessystem robustness, in that trigger events occurring at physiologic normsare avoided.

For example, the ranges of velocity and acceleration of a patient'sblood pressure should fall within some limits around zero (generally notsymmetric). Changes in mechanical coupling could also be observed aschanges (velocity or acceleration) in tonometrically observed pressure.The first process 100 focuses on those changes in mechanical couplingthat are both comparatively large and rapid, thus producing velocity oracceleration values that are not realizable from the patient's arterialpressure alone. The buffer of the present embodiment comprises that“cushion” between the range of measurable velocity and acceleration thatis naturally occurring (from patient's arterial pressure) and thetrigger threshold for the first process 100. It will be recognized,however, that such buffer or cushion may be at least partly obviatedthrough use of one or more sensors that specifically measure changes inmechanical coupling, such as for example a pad sensor, which would allowthe system to identify and possibly respond to smaller changes and/orlower frequency changes in mechanical coupling.

When sudden changes in mechanical coupling are detected, tonometricpressure data are compared for periods occurring before and after theprocess event. For instance, if the pulse pressure (defined for thepresent discussion as the difference between systolic and diastolicpressures) decreases from the maximum, or the mean pressure changessignificantly, then a limited scope pressure sweep is implemented toachieve the optimal applanation. If, despite this pressure sweep, acomparable pulse pressure is not achieved, then a reacquisition state(described in greater detail below) must be entered.

Note that in the present embodiment, the first process is active exceptin conditions where the system initialization, initial lateral searchand applanation sweeps are being performed or when operating in theaforementioned reacquisition state. The second process is also active atthe same time as the first process, except in conditions where the firstprocess is performing the limited scope pressure sweep as previouslydescribed. It will also be noted that during the limited scope pressuresweep, the current value of P_(T) is not displayed. Excessive periods,where the current P_(T) is not available limits the clinical utility ofthe device, as previously described herein with respect to the priorart. Thus, the present invention minimizes the need for the limitedscope pressure sweeps invoked by a process event, thereby improving theoverall performance and continuity of the technique over prior artsolutions.

The first process 100 of the present embodiment consists of 4 discretebut related states 102, 103, 104, 105 as illustrated in FIG. 1; (i)first state (“normal operation”) 102; (ii) second state (“event”) 103;(iii) third state (“recovery”) 104; and (iv) fourth state (“sweep”) 105.The impact of a process event on the servo control system (described ingreater detail below with respect to FIGS. 2 and 5), depends largely onthe then-exiting state. Each of these four process states 102–105 arenow described in detail.

(i) First (Normal Operation) State—The first state 102 is the initialand default operating state. This state is entered when a sweepcompletes, or following the detection of a sudden change in mechanicalcoupling little change was observed between pre- and post-pressure data.If a process event occurs, then the most recent median filteredtonometric mean and pulse pressures are stored for future comparisons. Atemporal parameter (e.g., Time_(—)of_(—)Last₁₃ Event) is set to zero(units in seconds), and the process state is set to the second state(event). If no process event is detected, the first state (normaloperation) is maintained. Note that in the present embodiment, thesecond process 200 (i.e., servoing, discussed below with respect toFIGS. 2–2 i) is active during this first normal operating state 102.

(ii) Second (Event) State—The second or event state 104 indicates thatone or more process events 106 has recently occurred, and the system iswaiting for the perturbations relating to the event(s) to subside beforeentering the next state. If a process event occurs then, the temporalparameter (e.g., Time_(—)of_(—)Last_(—)Event) is reset. However, if asufficient time ( i.e., 2 seconds) has elapsed since the last event (asdetermined by the existing value Time_(—)of_(—)Last_(—)Event), then thebeat counter (Beat_(—)Counter) value is initialized for comparisons, andthe process is set to the third (recovery) state. The prescribed timedelay of the present embodiment advantageously minimizes the risk ofcorrupted pressure data from being incorporated in the post-processevent pressure data. As in the first state described above, the secondprocess (servoing) is active during the second state 103.

(iii) Third (Recovery) State—Entry into this third state 104 indicatesthat the recent process event has subsided, and the system is collectingnew tonometric beat pressure data to compare with pre-perturbation data.Upon exit from the third state 104 and before entering the next state,if a process event occurs, then the Time_(—)of_(—)Last_(—)Eventparameter is reset, and the process state is set to the second (event)state 103 per step 108. Otherwise, if a new tonometric beat has beenidentified then, the system beat counter parameter (e.g.,Beat_(—)Counter) is incremented for comparisons, and new mean and pulsepressures are written to the storage device (FIG. 5) for subsequentcomparisons.

Note that if the beat counter has reached a predetermined thresholdvalue, then a comparison of the tonometric pulse and mean pressuresstored both before and after the triggering process event is performed.If, upon performing this comparison, the mean pressure has changedbeyond a predetermined threshold, or the pulse pressure has decreasedsubstantially from pre- to post-event, then the state of the process 100is set to the fourth (i.e., sweep) state 105, the sweep initializationparameter (e.g., Initialize_(—)Sweep) is set to “true”, and the secondprocess (servoing) is disabled. The motor position parameter (e.g.,Motor_(—)Position) is accordingly set to a target motor position value.Target motor position in the illustrated exemplary embodiment is set toeither 0 (fully retracted) or −50000 (fully extend out toward the radialartery) where units are motor steps. Target motor position is set to 0if the post-event mean pressure is greater than the pre-event meanpressure. Target motor position is set to −50000 if the post-event meanpressure is less than the pre-event mean pressure. If the mean pressurehas not increased beyond the threshold (and the pulse pressure has notdecreased substantially between pre- and post-event), the state of thefirst process 100 is set to the normal operating (first) state 102 perstep 110 of FIG. 1.

If the beat counter has not reached its predetermined threshold, thefirst process 100 remains in the third (recovery) state 104. As with thefirst and second states 102, 103 described above, the second (servoing)process 200 remains, in the illustrated embodiment, active during therecovery state 104.

(iv) Fourth (Sweep) State—Entry into this fourth state 105 indicatesthat the recent process event has caused a significant change in thetonometrically measured pulse pressure and/or mean pressure. Inresponse, the system performs a limited scope pressure sweep to resetthe optimal applanation level. Specifically, if the sweep initializationvariable (Initialize_(—)Sweep) is set true, the initial search directionas determined for target motor position in (iii) above, and theapplanation motor(s) are moved in the proper direction (rampcontinuously in the present embodiment, although other profiles may beused). Additionally, the sweep pressure memory is initialized, and the“first pass” parameter flag (e.g., FirstPass_(—)Flag) is set to “true.”

If a new beat has been identified, then the process appends thetonometric pressure data associated with the new beat to that existingin the memory array and the Beat_(—)Counter value is incremented forcomparisons. Specifically the data for each beat includes averageapplanation position, mean tonometrically measured pressure, systolictonometric pressure, diastolic tonometric pressure, and tonometric pulsepressure (i.e., systolic minus diastolic), which are stored inparameter-specific one dimensional arrays within memory.

If the measured mean pressure has reached its minimum goal and currentpulse pressure values (median filtered) are significantly less thanmaximum pulse pressures (median filtered) observed during the sweep,then additional analysis is performed. Specifically, if the maximumpulse occurred close to beginning of the applanation sweep, and thefirst pass flag (FirstPass_(—)Flag) equals “true” then theFirstPass_(—)Flag is set to “false”, and the applanation motor(s) aremoved, e.g., to ramp continuously, in the direction opposite from theprior direction of travel. If the maximum pulse pressure did not occurnear the beginning of the sweep, and if the maximum pulse pressure(median filtered) is a large percentage (e.g., 80% or greater in thepresent embodiment) of that occurring prior to the triggering event thenthe state of the process 100 is set to the first state 102, and servoingat the maximum pulse pressure is initialized. In the context of thepresent embodiment, the measured mean pressure reaching its “minimumgoal” comprises the median filtered mean pressure at least reaching andsearching beyond the pre event trigger mean pressure. Note that thisrequirement can be dependent on the direction of the search (i.e.,whether extending or retracting the sensor); specifically, the medianfiltered mean pressure is greater than the pre-event trigger meanpressure for the sensor extension case, or less than the pre-eventtrigger mean pressure for the retraction case.

However, if the maximum pulse pressure occurs not near the beginning,and the maximum pressure value is not a large percentage of the prioroccurring value, then the reacquisition process (the third process 400discussed below with respect to FIG. 4) is entered, and the firstprocess 100 is disabled.

It is also noted that second process 200 (FIG. 2) is not active duringthe fourth state 105 of the first process 100.

FIG. 1 a provides a detailed flow chart representation of the exemplaryfirst process 100 of FIG. 1.

It will further be recognized that the first process 100 may be appliedto blood pressure measurements irrespective of the mechanism used tooriginally attain optimal applanation position. In this scenario, thefirst process operates effectively as if a large transient event hadoccurred, and uses the foregoing method (in conjunction with the thirdor reacquisition process 400 described below with respect to FIG. 4) tosettle onto optimal positions for these parameters.

It will be recognized that as referenced above, the first process of thepresent invention need not operate using a “physiologic” parameter. Oneexemplary alternative approach of the present invention is to apply andaccelerometer or force transducer of the type well known in the art onor contiguous with the sensor surface; i.e., not necessarily over theblood vessel of interest itself. Similarly, such accelerometer ortransducer may be located on the apparatus coupling the sensor to thepatient (e.g., wrist brace or strap), or alternatively on the shaft (notshown) between the actuating mechanism and the sensor/pad (or within theactuating mechanism itself). Since the first process of the presentinvention fundamentally detects rapid motion corresponding to potentialmechanical coupling disruptions, literally any physical configurationand/or parameter which provides information relating to such motion anddisruptions may be used consistent with the invention. As yet anotheralternative embodiment, an optical sensor of the type well known in theelectronic arts may be positioned near the skin and accordingly used asthe mechanism to detect sudden changes in sensor/patient relativeposition.

It can be appreciated that the use of the tonometric pressure sensor asthe basis for measurement of the physical parameter (as described indetail above with respect to the exemplary embodiment) provides thebenefits of both simplicity and reduced cost by eliminating the need foran added sensor or added complexity of the actuating mechanisms.However, certain benefits relating to the decoupling of the parametersignal from the arterial pressure signal (as compared to the use of thetonometric pressure signal as described above) may be realized throughuse of one of the alternate embodiments set forth above. For example,use of a non-hemodynamic parameter allows for the separation ofmechanical coupling changes from the physiologic signal, since no (or atleast minimal) physiologic content exists in the measurements obtainedin this fashion. Furthermore, the use of non-physiologic parameter(e.g., pad force or pressure as measured by the force on the applanationmotor shaft as described above) allows the use of a much smaller bufferzone, since there is effectively no overlap in the frequency andamplitude of the pressure signal as measured by the pad relative to thepressure changes induced by disruptions in mechanical coupling.

Description of Second Process

Referring now to FIGS. 2–2 i, one exemplary embodiment of the method ofidentifying changes in the compression coupling and readjustment of theapplanation level back to optimal (i.e., “second process”) according tothe invention is described in detail. It will be appreciated that whilethe following discussion of the exemplary embodiment is cast primarilyin terms of the adjustment of the tonometric applanation level (i.e.,level of compression), the techniques of the present aspect of theinvention may be equally applied to the other spatial domains associatedwith the tonometric measurement environment; e.g., lateral position andproximal position. Such applications may be coupled to that associatedwith the applanation domain, or alternatively be entirely independent.

It will also be appreciated that while the following discussion is castin terms of an exemplary embodiment utilizing Pseudo Random BinarySequences (PRBS) generally complying with a structured sequence of theform (2^(n)−1), other white noise, random/pseudo-random, or pseudo-noise(PN) processes may be substituted with success, and hence the followingdiscussion is merely illustrative of the broader principles of theinvention. For example, as one alternative, a pseudo-random generationalgorithm of the type well known in the communications arts (such asthat used for example in generating FHSS hop or CDMA pn “long code”sequences) is seeded with a given initial seed value and generates apseudo-random sequence, the latter used to modulate the applanationlevel in the present invention. Other perturbations or sequences (anymovement surrounding the optimal applanation position including forexample sinusoidal perturbations) may also be substituted consistentwith the present invention; however, the methods described with respectto the exemplary embodiment above have inherently good signal-to-noiseratio (SNR) across the frequency band of interest.

FIG. 2 shows a logical flow diagram of the exemplary embodiment of thesecond process 200. The process 200 generally comprises first providinga transducer adapted for determining pressure (step 202). The transduceris disposed proximate to the blood vessel of interest (step 204), inorder to provide coupling of pressure signals from the blood vessel wallthrough the tissue and to the active surface(s) of the sensor. Note thatan intermediary coupling agent (such as a gel) may be used if desired.Next, an optimal or near-optimal state of vessel compression is achievedper step 206. It will be recognized that such compression may be appliedvia the pressure transducer itself, or alternatively via anothermechanism (such as a contact pad). The optimized level of compressioncan be determined using, inter alia, the methods of the aforementionedco-pending U.S. patent application Ser. No. 10/072,508 filed Feb. 5,2002. The level of compression applied to the blood vessel is nextvaried over time (step 208). In the illustrated embodiment, the act ofvarying the level of compression per step 208 comprises modulating thelevel of compression in comparatively small magnitude “perturbations”according to a modulation sequence having particular desirableproperties, although other schemes (e.g., non-sequential) may be used.The effects of the modulation on the observed pressure values (e.g.,pulse pressure, diastolic, etc.) are then observed per step 210, andcorrections in the level of compression applied to the blood vessel madeper step 212 based on the observed effects of the modulation sequence.

It will be appreciated that the second process 200 (and associatedapparatus) need not measure the applied pressure or compression, such asvia a force sensor or the pressure transducer). Rather, the presentembodiment is largely effects-based in that applanation level(compression) can be adjusted based simply on the observed effects ofthe modulation. Hence, the applanation mechanism can advantageously bemade “dumb”, thereby simplifying the mechanism as well as other aspectsof the system. However, if explicit monitoring of the applied force orcompression is desired, such intelligence can be utilized in conjunctionwith the invention as well.

As previously discussed, one clinical objective of the second process200 is to maintain the tonometrically observed mean pressure within agiven value (e.g., +/−10 mmHg) of the optimum tonometric pressure, whichproduces maximum pulse pressure. During the second process 200, both thepatient's arterial pressure and the mechanical coupling between thetonometric transducer and the underlying artery can change. Either typeof change introduces a variation in the tonometrically observedpressure. Hence, the present invention seeks to differentiate betweenphysiologically-induced changes (e.g., those stemming from the patient'sphysiology, such as for example due to the introduction ofpharmacological agents), and mechanical coupling changes in thetonometrically observed pressure. It also seeks to constantly correctfor the second type of change (i.e., change in the mechanical coupling).

Sudden changes in the mechanical coupling between the tonometricpressure transducer and the artery (i.e. acceleration or “bumping” ofthe transducer or the wrist) can be detected by several techniques, aspreviously described herein with respect to FIG. 1, as well as that ofFIGS. 4–4 a described below. Slower changes in the mechanical couplingmust be detected and corrected by other means.

One method of detecting and correcting slower changes in mechanicalcoupling involves perturbing the system by modulating the compression ofthe artery and observing the resultant changes in tonometricallymeasured pulse pressure. The method and degree of perturbation should beoptimized in accordance with the overall clinical objectives.

Accordingly, the Assignee hereof has developed exemplary clinicalobjectives for use in accordance with the exemplary process 200described herein. It will be recognized that these objectives are merelyillustrative, and may be adapted and modified as needed to particularclinical environments or desired levels of performance and accuracy.

(i) Display disruption—First, the disruption of the system pressuredisplay by the induced perturbation should be minimized. Noticeablediscontinuities in the pressure display and delays in transfer of thepressure signal to the patient monitor (e.g., based on a predeterminedcriterion such as delays of 0.1 seconds or greater) are unacceptable.

(ii) Responsiveness—The tonometrically observed pressure from 20 mmHg ofoptimum T-Line pressure to within 10 mmHg occurs in accordance with agiven period of time (e.g., 1 minute). From a clinical perspective,excursions beyond roughly 10–15 mmHg in mean tonometrically measuredpressure from the actual intra-vascular pressure (such as A-Linepressure) for extended periods, e.g., longer than 1–2 minutes, are oftenclinically undesirable. Although measurement error can occur, asreflected by prevailing FDA requirements for cuff accuracy (+/−5 mmHgmean error with a standard deviation of 8 mmHg), more frequent andlonger duration divergences between tonometrically sensed pressure andtrue intravascular pressure reduce the clinical desirability of adevice. Thus, a clinically useful system should operate such that itresponds with reasonable speed and accuracy to changes in mechanicalcoupling.

(iii) Device Limitations—Limitations exist relating to the motion of theapplanation motor of the system. These limitations include for examplelimits in the applied electrical power and resulting output (mechanical)power and torque, the control of wear over time (i.e., motor longevity),and limits in the motor velocity and acceleration which precludeinstantaneous (i.e. step) changes in applanation. From bench dataobtained by Assignee, diastolic pressure in representative patientschanges on average 7 mmHg per 1000 motor steps (within the range of 4–10mmHg per 1000 motor steps) at an applanation level near optimum.Furthermore, pulse pressure changes for the same individuals an averageof 8 mmHg per 1000 motor steps (ranging from 4–14 mmHg per 1000 motorsteps). One exemplary actuator and motor scheme utilized by the Assigneehereof suggests a maximum rate of about 1000 motor steps per second.Changes in actuator design to alleviate some of these limitations arenot considered. Hence, it can be inferred that maximum rates ofdiastolic and pulse pressure change of about 7 mmHg/sec and 8 mmHg/sec,respectively, can be achieved with the aforementioned exemplaryapparatus.

(iv) Variations in Pulse Pressure—The patient's pulse pressure is timevariant. As is well documented in the literature, arrhythmias canproduce cyclical changes in pulse pressure (i.e. pulsus alternans,wherein a succession of high and low pulses exist in such a manner thata low pulse follows regularly a high pulse, and this low pulse isseparated from the following high pulse by a shorter pause than thatbetween it and the preceding high pulse.) See, e.g., “Apparent Bigeminyand Pulsus Alternans in Intermittent Left Bundle-Branch Block”, LaszloLittmann, M.D., and Jeffrey R. Goldberg, M.D., Departments of InternalMedicine and Family Practice, Carolinas Medical Center, Charlotte, N.C.,USA, which is incorporated by reference herein. It is well documentedthat patient respiration can produce sizeable changes in pulse pressureas well. Hence, a perturbation and servo-control system would ideally belargely if not completely insensitive to cyclical and randomfluctuations in arterial pulse pressure.

In addition to the foregoing objectives and limitations, the propertiesof the tonometric measuring and control system must be determined. It iswell known that the insertion of so-called “white noise” into a systemis a useful means of identifying properties associated with that system.In the present context, the introduction of such white noise generates apattern which effectively cannot be produced by the patient physiology.The inputs to the system include applanation motor position, and the“system” is the tonometrically obtained pulse pressure as a function ofapplanation level. Cross-correlating the changes in applanation positioninduced by the white noise with the resultant observed pulse pressureproduces a relationship between the applanation motor position and pulsepressure. This relationship is advantageously quite robust in thepresence of random or periodic fluctuations in pulse pressure, duelargely to the insertion of the white noise.

However, several considerations exist with respect to the practicalimplementation of white noise modulation of applanation motor positionin the present invention. First, true “white noise” assumes a normal orGaussian distribution of motor position. Such normal distributions cancontain very large excursions from the mean albeit with increasinglyless frequency (theoretically not bounded), whereas in contrast themotor position in the physical implementation of the present inventionis bounded.

Second, the time to travel from one position limit to the other (if suchtravel is needed) is significant, as previously discussed with respectto maximum motor rate. Instantaneous changes in applanation mechanismposition are therefore not possible.

Third, white noise identification theoretically requires an infiniteperiod time for convergence, even approximations of which are notpractical in the clinical setting. Ideally, a useful clinical devicewould employ control systems which would converge in a very short periodof time, thereby enhancing the continuity of the tonometric pressuremeasurement.

As is known in the mathematical arts, Pseudo Random Binary Sequences(PRBS) are a defined sequence of inputs (+/−1) that possess correlativeproperties similar to white noise, but converge in within a give timeperiod. In addition, the inputs can be specified (and thereby optimized)to produce more effective signal-to-noise ratio (SNR) within theconstraints of the system. One common type of PRBS sequence generatoruses an n-bit shift register with a feedback structure containingmodulo-2 adders (i.e. XOR gates) and connected to appropriate taps onthe shift register. The generator generates a maximal length binarysequence of according to Eqn. 3:maximal length binary sequence=length(2^(n)−1).  (Eqn. 3)The maximal length (or “m-sequence”) has nearly random properties thatare particularly useful in the present invention, and is classed as apseudo-noise (PN) sequence. Properties of m-sequences commonly include:

-   -   (a) “Balance” Property—For each period of the sequence, the        number of '1's and '0's differ by at most one. For example in a        63 bit sequence, there are 32 '1's and 31 '0's.    -   (b) “Run Proportionality” Property—In the sequences of '1's and        of '0's in each period, one half the runs of each kind are of        length one, one quarter are of length two, one eighth are of        length three, and so forth.    -   (c) “Shift and add” Property—The modulo-2 sum of an m-sequence        and any cyclic shift of the same sequence results in a third        cyclic shift of the same sequence.    -   (d) “Correlation” Property—When a full period of the sequence is        compared in term-by-term fashion with any cyclic shift of        itself, the number differences is equal to the number of        similarities plus one (1).    -   (e) “Spectral” Properties—The m-sequence is periodic, and        therefore the spectrum consists of a sequence of equally-spaced        harmonics where the spacing is the reciprocal of the period.        With the exception of the dc harmonic, the magnitude of the        harmonics are equal. Aside from the spectral lines, the        frequency spectrum of a maximum length sequence is similar to        that of a random sequence.

Accordingly, detecting and correcting slower-rate changes in mechanicalcoupling as previously described can be accomplished by applying PRBSmodulation of the applanation position, and observing the resultantchanges in tonometrically observed pulse pressure. In one exemplaryembodiment of the present invention, the physical implementation of sucha system contains three interactive “components”: (i) a modulator; (ii)a signal restoration entity; and (iii) an identification/servo controlentity. It will be recognized by those of ordinary skill that the term“entity” as used herein relates to any number of a wide variety ofimplementations, ranging from a corporeal entity (e.g., electronics andassociated integrated circuits) to a completely virtual or intangibleone (e.g., one manifest in the form of algorithms, routines, or softwareobjects or components resident across the various hardware environmentsof a system).

The following exemplary description illustrates the operation of theaforementioned multi-component system according to one embodiment of theinvention.

Referring now to FIGS. 2 a–2 c, the characteristics and response of anexemplary patient are described. As shown in FIG. 2 a, the patientexhibits a given pulse pressure versus diastolic pressure relationship230. The maximum pulse pressure 232 (e.g., 42 mmHg in the illustratedexample) occurs at a diastolic pressure of about 75 mmHg 234.

Furthermore, it is assumed for purposes of illustration that theapplanation motor is held at a constant position (at the point ofoptimal compression corresponding to maximal pulse pressure), and thatthe patient has a time-invariant arterial pressure with a heart rate of60 bpm with the shape 236 shown in FIG. 2 b. If the patient's artery isnot sufficiently compressed, a lower diastolic pressure 237 (e.g.,diastolic pressure=67 mmHg in this example) will result, as indicated bythe “sub-optimal” waveform 238 of FIG. 2 c. Note that the pulse pressure(systolic minus diastolic) at a tonometrically measured diastolicpressure of 67 mmHg is only approximately 36 mmHg. Under this condition,the system must identify the fact that the artery is under-compressedand adjust the applanation level appropriately over time.

Referring now to FIGS. 2 d–2 e, the modulation entity of the servoprocess 200 of the invention is described in the context of theforegoing example. The modulator of the present embodiment introduceschanges in artery compression (applanation position) over a limitedrange around the “optimal” operating point. These changes are in thepresent embodiment synchronized with the downward slope of the arterialpressure waveform, this downward slope being associated with diastolicrelaxation of the heart. Other synchronizations (or even lack ofsynchronization) may be used if desired, however. The modulationsinduced by the modulation entity ramp the applanation mechanism positionfrom one extreme to an equal and opposite extreme (e.g., 400 motor stepsin the present embodiment) around the operating point over a briefperiod (e.g., 0.5 seconds), although other profiles (symmetric ornon-symmetric) and durations may be substituted if desired. The decisionto move from one extreme to another is controlled in this embodiment bya Pseudo Random Binary Sequence (PRBS) of the type previously described.This modulation scheme produces changes in pressure offset, and mayproduce highly correlated changes in pulse pressure.

In the illustrated embodiment, a PRBS sequence of length=7 isimplemented (i.e., 1,1,1,−1,−1,1,−1) to modulate the pressure waveformas shown in FIG. 2 d. Note that for the clinical application, therespiratory period of the patient, and its corresponding cyclicalfluctuations in pulse pressure, approximates the repetition period ofthe PRBS of length 7. Hence, clinical embodiments of the applicationincorporate a PRBS of appropriate length such as length=15 (i.e., 1,1,−1, 1,−1, 1, 1, 1, 1, −1, −1, −1, 1, −1, −1) or length 31 (i.e.,1,1,1,1, −1,1,1, −1,−1, 1, 1, 1,−1, −1, −1, −1, 1, 1, −1, 1, −1, 1,−1,−1, 1, −1, −1, −1, 1, −1, 1) Specifically, the PRBS sequence repeatsevery 7, 15, 31 beats if one does not allow for transition beats, and inthe exemplary case 11, 22, or 47 beats respectively allowing fortransition beats. Any noise source that repeats in the same time base(sinusoidal noise frequency) will have a greater impact on systemperformance than noise sources with other frequency content. Respirationperiod occurs in the range of 5–7 seconds; hence, during this period,anywhere from 4–14 heartbeats could be observed. Thus, a PRBS sequenceof length 7 with an effective length 11 when transition beats areincluded falls directly within the respiration period. The longersequences do not have that problem. Conversely, however, the noiserejection properties require a complete cycle of data for properfunction. Hence, control using sequences that are excessively long areprone to sluggish control, thereby detracting from system performance.

FIG. 2 e depicts the practical implementation of PRBS changes inapplanation level. Practical mechanical considerations relating to theapplanation motor preclude step changes in applanation level ofsufficient magnitude to produce a significant change (e.g., 6 mmHg) inobserved tonometric pressure. Thus, for the present embodiment, theapplanation position is ramped over a period of time (e.g., 0.5seconds), as shown in the PRBS portion 239 of FIG. 2 e. Since noguarantee exists that the ramp will complete by the end of the beat, avariable delay in the PRBS, which is a function of heart rate and numberof motor steps traveled, is included within each transition periodwithout loss of the correlative properties. Typically this delay is 1heart beat. but at high heart rates could extend to two and possiblymore beats. It is noted that the PRBS portion 239 of FIG. 2 e isdimensionless. In effect, two classes of beats are created in thepresent implementation; “measurement” beats and “transition” beats. Whenthe motor is moved, transition beats are added (e.g., for a length=15sequence, 7 or 8 transition beats are added).

Referring now to FIGS. 2 e and 2 f, the signal restoration entity of theinvention is described in detail. As shown above, the modulation entitywill introduce changes in the measured pressure waveform. These changesin the pressure waveform may be disruptive to the clinician undercertain circumstances. Note that the PRBS-modulated pressure waveform240 of FIG. 2 e varies significantly around the tonometric pressure 242that would otherwise be observed if the PRBS or other modulation was notactive. Hence, the signal restoration entity must anticipate the changesin the observed tonometric pressure waveform introduced by themodulation entity, and (mathematically or otherwise) restore themodulated waveform to a shape that is clinically equivalent to theun-modulated tonometric waveform.

Specifically, by implementing a linear ramp during the period when themodulation is active, the original un-modulated waveform can berestored. This process assumes the amount of change that is observed bythe modulation is not large (e.g.,< roughly 6 mmHg in the illustratedembodiment) and is adaptively identified (i.e., the cross-correlation ofthe PRBS modulation sequence and diastolic pressure from which theaverage diastolic pressure has been removed can be used to provide anestimate of the expected change in pressure produced by the modulation).

Note that the foregoing process in essence adds or subtracts a pressurecorrection offset to the measured pressure. When the modulation entailsextension of the sensor from the mechanism (in the exemplaryembodiment), the pressure offset correction is subtracted from themeasured pressure data, and vice-versa. The value (units in mmHg) of theoffset correction can not be directly determined unless compared with asource of true intravascular pressure (e.g., A-Line, thus defeating thepurpose of the tonometric sensor), but it can be estimated by evaluatingthe change in diastolic, systolic, mean, pulse, or similar pressurevalues correlated to the change in motor position. Thus, for example,the cross-correlation between the PRBS and the diastolic pressures (meanpressure removed) can be used to estimate the offset correction. Thisestimate can be updated with each new beat producing a continuousestimate of the offset correction. Note that during applanation motorramping, the offset correction of the exemplary embodiment also rampsfrom one extreme to the other. Additionally, it will be recognized thatthe amount of modulation (e.g., number of motor steps in the illustratedembodiment) can be adjusted to produce the desired amount of pressurechange. In the present embodiment, the modulation level is continuouslyadjusted to achieve 5 mmHg peak-to-peak excursion subject to a limit;i.e., provided that the peak-to-peak excursion is limited to between 50and 800 motor steps. Other modulation schemes and limits can be usedconsistent with the invention, however.

Note that lead/lag relating to the assumed start of the motor movement(as opposed to the actual start of movement), and the introduced changesin pressure, can lead to small artifacts or “bumps” in the pressurewaveform display; however, these are often imperceptible to theoperator, and advantageously no points of discontinuity exist in thedisplay, unlike prior art systems.

Errors between the actual and predicted pressure change (i.e., thosepredicted by the signal restoration entity relating to the appliedmodulation) are exhibited as small jitter synchronized with the PRBS inthe diastolic pressure display. FIG. 2 f depicts the “restored” waveform242; i.e., the waveform(s) of FIG. 2 e after correction by therestoration entity. Note that the error produced by the linear rampapproximation is small compared to both (i) the pulse pressure, and (ii)pixel resolution of the monitor. Thus, the process of restoring aclinically equivalent waveform is readily achieved using the techniquesdescribed herein.

Referring now to FIGS. 2 g–2 i, the identification/servo control (ISC)entity of the present embodiment is described.

As shown in FIG. 2 f, the corrected (“restored”) pulse pressure valuesassociated with points on the restored waveform 242 fluctuate aroundcorresponding ones of the nominal, non-modulated sub-optimal applanationwaveform 238. Further, it will be recognized that these fluctuations,albeit comparatively small in magnitude, generally correlate with themodulation in applanation level, as illustrated by FIG. 2 g.

The ISC entity of the present embodiment takes advantage of thecorrelative properties of white noise. As shown in FIG. 2 g, anauto-correlation of the PRBS modulation is performed. Theauto-correlation of the PRBS signal has a gain equal to the PRBS length(e.g., 7) for zero phase delay, and negative unity gain for other phasedelays until the PRBS repeats. The PRBS modulation, time synchronizedtonometrically measured pulse pressure, and un-corrected diastolicpressures for the preceding example are displayed in Table 2. Note thatthe PRBS values labeled “T” indicate transition beats where theapplanation motors are still in the process of ramping from one positionto the next. These beats are removed from the subsequentcross-correlation without loss of the correlative properties of thePRBS.

TABLE 2 Pulse Un-Corrected Beat PRBS Pressure Diastolic Pressure 1 1 3870 2 1 38 70 3 1 38 70 4 T 35 66 5 −1 34 64 6 −1 34 64 7 T 37 68 8 1 3870 9 T 35 66 10 −1 34 64 11 T 37 68 12 1 38 70 13 1 38 70FIG. 2 h illustrates the weighted zero-mean values for pulse pressureand diastolic pressure (after removing the “transition” (T) beats) forthe first 7 beats, and synchronized to the PRBS modulation. It will benoted that the pulse pressure values 250 and diastolic pressure values252 are well correlated with the PRBS modulation of applanation level254.

Performing the cross-correlation between the PRBS modulation ofapplanation and the pulse and diastolic pressures produces a largesignal at phase delay=0, as shown in FIG. 2 i. For diastolic pressure,the change induced by the modulation equals 21 mmHg divided by the PRBSlength= 21/7=3 mmHg. This means that the modulation process (extendingthe sensor out from operating point “0” during the modulation) caused a3 mmHg increase in diastolic pressure. The total excursion (fromPRBS=“−1” to PRBS=“1” thus equals 6 mmHg (70 mmHg−64 mmHg) using thetable above. Similarly, the modulation-induced change in pulse pressureas shown in FIG. 2 i equals 14/7 or 2 mmHg. Thus, the system recognizesthat increasing compression (applanation) will increase the observedpulse pressure. Subsequently, the control system can change theoperating point (applanation motor position around which PRBS modulationoperates) appropriately to maintain optimal coupling. Using thisapproach, the control system can accurately track on a beat-by-beatbasis the motor position corresponding to the applanation level thatproduces maximum pulse pressure.

A circular buffer arrangement is used in the exemplary embodiment of theapparatus implementing the foregoing technique; this advantageouslyallows the calculation to be updated once per beat. It will berecognized, however, that other arrangements may be used to implementthe desired functionality.

It will also be recognized that the techniques described above withrespect to the second process may be equally applied to the otherdomains of spatial variation; i.e., the lateral and/or proximal searchalgorithms with proper selection of random/pseudo-random sequence (e.g.,PRBS) parameters, thereby providing continuous tracking in the selecteddirection(s) as well as in the application domain. Such application andselection are readily implemented by those of ordinary skill given thepresent disclosure, and accordingly are not described further herein.

Based on observations and testing performed by the Assignee hereof, theperformance of the present invention may be further enhanced undercertain circumstances by the inclusion of one or more optional controland signal processing features; use of these features can enable thesystem to respond more quickly to an event by, inter alia, mitigatingcontrol overshoot and/or eliminating unwanted noise and other artifactsfrom the processed signals(s). These features include: (i) Hampelfiltering of pulse and diastolic pressures; (ii) the addition of aproportional component to the control (servo) loop; (iii) the adjustmentof integral control of the servo loop through estimation of the SNR; (v)increasing the precision of the diastolic cross-correlation; (vi)control of the initial settings for the diastolic pressurecross-correlation arrays; (vii) adjusting the integral gain based on theaverage pulse pressure; and (viii) correcting for BMI or other scalingartifact. Each of the foregoing features are now described in detail.

(i) Hampel Filter for Pulse and Diastolic Pressures—Improperly detectedbeats, noise, and cardiac arrhythmias can introduce large one-timechanges in pulse pressure measurements that are not reflective of theapplanation state of the patient. In the context of the second process200 described above, these beats can potentially disrupt the feedbackcontrol. One exemplary method of removing most of these beats comprisesindependently applying a Hampel filter of the type well known in thesignal processing arts to each of the positive PRBS pulse pressure andnegative PRBS pulse pressure values in the respective arrays. The Hampelfilter is advantageously employed as opposed to other filteringtechniques including low pass filters or median filters which increasethe time lag in the servo control loop.

(ii) Addition of Proportional Component to Servo Loop IntegralControl—The PRBS-based algorithm described above operates generally as asophisticated block filter with a lag equal to ½ of the PRBS length. Inthe second process 200, transition beats (PRBS length/2) are added tothe computation, thereby creating a lag (e.g., 11.25 beats in the aboveexample) from a change in coupling to its full impact to itsidentification through the cross-correlation with the PRBS andsubsequent servo control. This lag can produce an overshoot in theintegral servo control system when recovering from a manually introducedstep change in artery compression (such as may be experienced when theNIBP measurement apparatus is jarred), and the integral gain is set toolarge. Adding a proportional component to the servo control algorithmand retuning the integral control gain advantageously reduces themagnitude of this overshoot. Since the servo control system operatesbased on changes in the “target” applanation level, a proportionalcontrol component may take the form of Eqn. 4 below:M _(TP)(t)=K _(p)*(X _(corr) [t]−X _(corr) [t−k])  (Eqn. 4)where M_(TP)(t) is the new target applanation motor position, X_(corr)is the 0^(th) delay of the cross-correlation of the PRBS and zero meanpulse pressures, t is the current pulse, and k is the number of beatspast. In one exemplary embodiment, values of (k=3) and K_(p)=1x(integral gain) are utilized.

(iii) Integral Control of the Servo Loop by Estimating SNR—The non-zeroterms of the aforementioned cross-correlation provide some indication ofthe noise potentially present in the pulse pressure estimates. Adding a“governor” to the servo control system which is triggered upon attainingone or more predetermined criteria; e.g., when the non-zero terms(average absolute or maximum absolute) are a percentage of the 0^(th)term, can decrease the sensitivity of the system to such noise. Forexample, a manually introduced step change in artery compression canintroduce a large change in the operating state (see discussion of thefirst process 100 above), which can drive the initial recovery from theevent in the wrong direction until the aforementioned identification lagis overcome. Meanwhile, the non-zero elements of the cross correlationalso become large until the lag is also overcome. The governor mechanismdescribed herein mitigates the effects of these non-zero elements duringthe lag period.

(iv) Improved Precision on Diastolic Cross-Correlation—As describedabove with respect the “nominal” embodiment of the present invention,cross-correlations are performed between the diastolic pressure and thePRBS component. The accuracy of these cross-correlation calculations maybe increased by using the time varying signed modulation signal as thebasis of the cross-correlation, rather than the PRBS as previouslydescribed. When the signed modulation signal is implemented, thecross-correlation value is divided by the average absolute modulationsignal for the period under consideration; otherwise, the servoadjustment to subsequent modulation counts and operating applanationposition may be adversely impacted.

(v) Control of Initial Settings for Diastolic Pressure Cross-CorrelationArrays—To provide an initially reactive system and to speed initialconvergence, the nominal system is initialized to provide comparativelylarge modulations. On some patients, however, the modulation (measuredin the present context in terms of “motor delta” which is defined as theestimated absolute change in applanation motor position in stepsrequired to change end diastolic pressure by a pre-determined quantitysuch as 2.5 mmHg) is initially excessive; e.g., up to 8 or 10 times thenumber of motor steps otherwise required. If motor delta is set toolarge, then the applanation motor will initially move much farther thannecessary/desired during PRBS, and the patient's diastolic pressure willchange much greater than anticipated. Waveform reconstruction will notsufficiently compensate for changes in diastolic pressure, thus shiftsor oscillations in diastolic pressure will be noticeable on the pressuredisplay, which is undesirable. Nonetheless, the large motor delta willaid in the rapid convergence to the applanation position correspondingto maximum pulse pressure. On the contrary, if the motor delta is settoo small, then applanation will not sufficiently excite the system,thus slowing convergence to the applanation position corresponding tomaximum pulse pressure. Meanwhile, the restoration process willovercompensate for the change in diastolic pressure with PRBSmodulation, and produce noticeable shifting in the displayed pressure.

To address this issue, the initial modulation level can be controlled,such that a predetermined maximum number of steps (e.g., 150) areutilized, or alternatively by applying a more sophisticated technique ofdetermining the optimal initial modulation as illustrated in FIGS. 3–3b. Specifically, the initial applanation pressure sweep providessufficient data to estimate the necessary motor delta to changediastolic pressure by a predetermined amount (e.g., 2.5 mmHg). The sweepdata is first obtained (step 302 of FIG. 3), and is used to generate thearray of diastolic pressure data values, aiDiastoleP[ ], and the arrayof applanation position, alAppPos[ ], for all the beats in the sweep(step 304). At the end of the applanation sweep process, the beat whichprovided the maximum pulse pressure is identified as iSysPointer (step306).

In one exemplary embodiment of the method 300, outlying or abhorrentvalues are first removed from alAppPos[] and aiDiastoleP[] via a Hampelfilter of the type well known in the art, using for example a 3- or4-standard deviations (σ) outlier test or comparable mechanism (step308). Other filter types can also be substituted, as will be appreciatedby those of ordinary skill.

Next, in step 310, those beats whose diastolic pressure ranges from thatassociated with the optimum beat minus a predetermined value (e.g., −10mmHg) to that corresponding to optimum beat plus the predetermined value(+10 mmHg) is determined.

The slope of the diastolic pressure/applanation position curve (in unitsof mmHg per motor step in the present embodiment) over that region ofinterest is next determined in step 312. This provides in effect asensitivity of diastolic pressure to motor position.

In step 314, the slope value(s) determined in step 312 are used tocalculate the number of applanation motor steps required to change thediastolic pressure by a desired amount (e.g., motor delta=2.5/slope inthe illustrated embodiment). In the illustrated embodiment, the PRBSprocess is simply a method of determining the slope around the nominal.

Lastly, in step 316, the motor delta value is bounded within acceptablelimits which will reduce initial “overstepping” of the modulation aspreviously described. For example, in one embodiment, the allowedinitial motor delta value is bounded on the low end by 40 motor steps,and on the high end by 400 motor steps.

It will also be recognized that a similar issue (i.e., “overstepping”)may arise when initiating an applanation sweep subsequent to the firstprocess 100 described above with respect to FIG. 1. Accordingly, theaforementioned methods of mitigating excessive modulations can beemployed in this context as well.

(vii) Gain Adjustment Based on Average Pulse Pressure—Adjustments tointegral gain (i.e., autocorrelation gain with zero phase delay) is inthe above-described embodiment independent of the underlying averagepulse pressure, as reflected in the following relationship:M _(TP)(t)=(K _(i) *K _(pp) [t]*K _(n) [t]*X _(corr) [t])+M_(TP)(t−1)  (Eqn. 5)where M_(TP)(t) is the new target applanation motor position,M_(TP)(t−1) is the previous target applanation motor position, X_(corr)is the 0^(th) delay of the cross-correlation of the PRBS and zero meanpulse pressures, t is the current pulse, K_(i) is the fixed integralgain, K_(pp)[t] is the integral gain modifier that is inversely relatedto pulse pressure, and K_(n)[t] is the integral gain modifier that isrelated to the signal-to-noise ratio.

Thus, as an example, a pulse pressure cross-correlation of magnitude 2has the same control “impact” at an average pulse pressure of 60 mmHg asit does at 20 mmHg. Making the value of this gain quasi-inverselyproportional to the underlying average pulse pressure makes the controlsystem more responsive both for individuals with low pulse pressure, andfor all individuals when the system is not situated close optimum. Itwill be recognized that the foregoing coupling between the integral gainand pressure may take on other forms as well. For example, the gainadjustment need not be proportional or quasi-proportional, but rathermay be based on a limited number of continuous or non-continuousdiscrete pressure ranges if desired (e.g., 0–10 mmHg,>10–<25 mmHg,etc.), or made deterministic upon other measured or observed parameters.Furthermore, the gain adjustment may be coupled to underlying criteriaother than pulse pressure; e.g., diastolic or systolic pressure, meanpressure, blood flow velocity or kinetic energy, vessel diameter, bodymass index, etc.

(viii) Correction for Scaling on Observed Pressure Waveforms—Clinicalobservations made by the Assignee hereof indicate that under somecircumstances, limited changes in the pressure displayed to the operatormay be induced in part by the modulation occurring during the secondprocess 200 described above. One cause of this behavior relates to theinteraction of the pressure waveform restoration and scaling (e.g., BMI)algorithms with changing mean pressures. To address this behavior, analternate scaling implementation may be used. Specifically, thehigh-pass filter (HPF) component of the pressure waveform (2 ^(nd) order0.25 Hz cutoff frequency) is scaled, and combining the HPF componentmultiplied by the scaling factor (e.g., BMI scale factor) with the rawpressure waveform to produce the scaled pressure waveform.

It will be recognized that the foregoing features (i)–(viii) are purelyoptional in nature, and may be selected by the system designer at timeof apparatus design and manufacture based on the anticipatedapplications. Alternatively, production devices may incorporate thefunctionality for each enhancement (as well as others), with theend-user having the ability to select which features they wish to employin particular applications (such as via a GUI configuration menu, API,or similar mechanism).

As yet another alternative, the production device may be configured toautomatically or adaptively determine if particular performanceenhancements should be utilized. For example, during start-up ormonitoring, the device may be configured to institute or “turn on” agiven feature or group of features, monitor the effects on the outputdata in light of prior data collected while the enhancement feature(s)were inoperative, and then decide which if any features should beutilized and under what conditions. As a simple example, consider wherethe Hampel filter (Item (i) above) is applied over time to the PBRSpulse pressure at times where sudden change in values are expected(i.e., start or re-entrance into the servo control system). The systemmay be programmed to disable the Hampel filter during these periods ofservo control or during the period immediately following an ipsilateraloscillometric cuff deflation.

Hence, the present invention contemplates the use of innate“intelligence” within the device hardware and software adapted toselectively control the application of one or more enhancement featuresduring device operation. Such innate control can be readily implementedby those of ordinary skill given the present disclosure, and accordinglyare not described in greater detail herein.

Interaction of First and Second Processes

The first process 100 and second process 200 described above are in theexemplary embodiment adapted to operate in concert with each other. Asdiscussed, the first process 100 responds to sudden changes inmechanical coupling between tonometric sensor and the underlying arterywhile the second process is designed to, inter alia, counteract lowerfrequency drifting in the mechanical coupling. Generally speaking, themore quickly that the second process 200 can respond to changes inmechanical coupling, the less restrictive the constraints that areplaced on the performance of the first process 100. With the presence ofthe second process 200, the first process 100 need not be reactive tosmall mechanical coupling changes; the second process 200 can be used toprovide recovery without the need to disable current pressure displayfor any period of time to perform the limited pressure search.

Accordingly, the following comprise exemplary values for variousparameters used by the first and/or second processes of the invention,which are “tuned” so as to provide maximum efficiency and efficacy ofthe two processes when they are both present in a given system. It willbe readily apparent that other values (and in fact parameters) may besubstituted depending on the particular application(s) in which they areapplied.

(i) Tonometric Pressure Velocity and Acceleration Triggers used withfirst process 100:

POS_(—)VEL_(—)TRIGGER=45 mmHg:

-   -   (45 mmHg/3 samples)*(160 Sample/1 Second)=2400 mmHg/sec        NEG_(—)VEL_(—)TRIGGER=−20 mmHg:    -   (−20 mmHg/3 samples)*(160 Sample/1 Second)=−1067 mmHg/sec        POS_(—)ACCL_(—)TRIGGER =15 mmHg:    -   (15 mmHg/3 samples)*(160 Sample/1 Second²)=800 mmHg/sec²        NEG_(—)ACCEL_(—)TRIGGER=−12 mmHg:    -   (−12 mmHg/3 samples)*(160 Sample/1 Second²)=640 mmHg/sec²        MEAN_(—)PRESSURE_(—)CHANGE_(—)TRIGGER=8 mmHg

(ii) Event trigger comparison of tonometric mean and pulse pressures offirst process 100:

PULSE_(—)RANGE_(—)PERCENT=10; a 10% decrease in decrease in tonometricpulse pressure triggers a limited pressure sweep (fourth state 105).

MEAN_(—)RANGE_(—)PERCENT=10; a 10% change in tonometric mean pressureand +/−8 mmHg change in mean pressure triggers a limited pressure sweep(fourth state 105).

Note that the second process 200 is in the exemplary embodiment madeactive when first process 100 is active in either the first state 102,second state 103, or third state 104 of the first process 100. TheAssignee hereof has also determined that under certain circumstances,scrubbing or elimination of the beats immediately surrounding a firstprocess event from use in the second process 200 may be helpful, sincethe measurement of mean pressure and pulse pressure for beatssurrounding the process event are corrupted.

Additionally, the exemplary embodiment renders the second process 200inactive when the first process 100 is active in its fourth state 105.The applanation motor position variable is set to the target positionupon entry into this fourth state 105, and the second process 200 isreinitialized upon return of the first process 100 from its fourth state105 to its first state 102.

The second process 200 can also be called from within the first process100 using any one of a number of well known software call routines inresponse to each new heart beat, and in concert with the previouslydescribed first process states 102–105 and initializations.

Additionally, the tonometric pressure velocity and acceleration triggers(i.e., POS_(—)VEL_(—)TRIGGER, NEG_(—)VEL_(—)TRIGGER,POS_(—)ACCL_(—)TRIGGER, and NEG_(—)ACCEL_(—)TRIGGER) associated with thefirst process 100 can be increased to provide a larger buffer betweennormal physiologic changes in pressure and trigger levels, as follows:POS_(—)VEL_(—)TRIGGER=50 mmHg; NEG_(—)VEL_(—)TRIGGER=−25 mmHg;POS_(—)ACCL_(—)TRIGGER=20 mmHg; and NEG_(—)ACCEL_(—)TRIGGER=−15 mmHg.

Furthermore, the checks of beat-to-beat changes in mean pressurepreviously described with respect to the first process 100 may beeliminated when the two processes 100, 200 are used concurrently. Thesemean pressure checks are designed primarily for use as protectionagainst slow changes in mechanical coupling (via periodicsweep-calibration) when the first process 100 is used in a stand-aloneconfiguration (i.e., without the presence of the second process 200).The presence of the second process 200 obviates the need for thiscomponent, and thereby also possible false first process events causedby arrhythmias (i.e. pulsus alternans) and other physiologic events.

Concurrent use of the first and second processes 100, 200 alsoadvantageously allows more frequent use of “tuning” comparisons betweenpre- and post-event values of tonometrically measured mean and pulsepressures associated with the first process 100. This feature reducesthe frequency of periods where disabling or freezing of the display ofcurrent pressure is required to perform the limited applanation sweeps,by simply allowing the second process 200 to recover from these smallerchanges in mechanical coupling. Exemplary values are as follows:PULSE_(—)RANGE_(—)PERCENT=20; and MEAN_(—)RANGE_(—)PERCENT=20.

It will also be recognized that while the foregoing exemplary embodimentof the second process 200 is interactive with the first process 100, thesecond process may operate independently of the first. For example, thesecond process may be used to adjust and/or maintain the desiredapplanation level (or position in the case of lateral and proximalcases) irrespective of the methodology used to initially determine theoptimal applanation/position. In effect, the second process 200 of theinvention used without the first process 100 will hunt and eventuallyconverge on the optimal position itself. This approach, however, hasbeen found by the Assignee hereof to be less temporally efficient thanthe approach previously described (i.e., determining optimal using theinitial sweep process), but may none-the-less be desirable in certaincircumstances where hardware/software simplicity can be traded forlonger acquisition and settling times. Hence, the present inventionshould in no way be considered to be restricted to embodiments whereinboth first and second processes 100, 200 are employed.

Third Process

Referring now to FIGS. 4 and 4 a, the third process of the exemplaryembodiment of the present invention is described.

During patient monitoring mode, the second process 200 previouslydescribed is capable of controlling the applanation of the sensor/padagainst the subject artery and overlying tissue, thereby compensatingfor slow changes (drifts) in the mechanical coupling between thesensor/pad and the underlying tissue. Furthermore, the second process200 can be most effective over applanation ranges where the pulsepressure is strong (higher signal-to-noise ratio), which exist near theoptimal applanation position. However, for large shifts in themechanical coupling between sensor/pad and the tissue (i.e. flexing ofthe wrist), the second process 200 may require several minutes toapplanate to the proper level to maximize tonometric pulse pressure.Thus, an opportunity exists to improve the performance of the system asa whole by detecting shifts in mechanical coupling that would incur anextended recovery period, and implement a more direct recovery process.The exemplary embodiment of the third process 400 shown in FIG. 4therefore takes a recovery “shortcut” as it were in those limitedcircumstances where recovery via the second process 200 would require anundesirably long time.

Thus, an important goal of the third process 400 of the presentinvention is to detect rapid shifts in mechanical coupling that inducesizeable error in pulse pressure and/or diastolic pressure, andimplement an optimal recovery approach.

In a first exemplary embodiment, the third process 400 is operated inconjunction with the first process 100 previously described.Specifically, the third process 400 operates during the first state 102of the first process 100 (see FIG. 1), and triggers the fourth state 105when an appreciable shift in the mechanical coupling is detected.Advantageously, the approach to detecting rapid shifts in couplingdescribed herein does not require any significant mechanical orelectrical changes to the system. The approach is based on identifyingchanges in tonometric pressure over a comparatively short period of timethat jointly are of the nature and degree to not likely occurphysiologically. Such changes also indicate that the second process 200might require significant time to properly recover. For example, when apatient's diastolic pressure increases, pulse pressure typically remainsconstant (or increases). Thus, detecting changes in pressure wherediastolic pressure increases and pulse pressure decreases significantlyover a short time period can be used to detect rapid shifts inmechanical coupling. Furthermore, episodes where the pulse pressureeither remains constant or increases are not problematic regardless ofthe change in diastolic pressure. Since the pulse pressure remains verystrong, the probability that the second process 200 can adjust theapplanation level (if necessary) within a reasonable period of timeremains high.

In the exemplary embodiment of FIG. 4, the process for detecting rapidshifts in mechanical coupling (third process 400) employs one or moremetrics for detecting joint shifts in parameters. In the illustratedembodiment, diastolic pressure and pulse pressure are used as thereferenced parameters, although it will be appreciated that otherparameters (physiologic or otherwise) may be substituted consistent withthe invention.

On exemplary scheme for detecting rapid shifts in mechanical coupling isdepicted in FIG. 4 a. The process 400 investigates changes in thecurrent block averaged pulse and diastolic pressures from “qualified”block averaged pulse and diastolic pressures from moving windows (e.g.,both 12 beats and 24 beats in the past in the illustrated embodiment).If the pulse pressure decreases and diastolic pressure deviates from theprevious diastolic pressures (12 or 24 beats past), then fourth state105 of the first process 100 is triggered.

Note that FIG. 4 a depicts a percentage change in pulse pressure (theselected parameter). Calculations may also be performed based uponchange in absolute blood pressure (mmHg), where for example 40 mmHg isequivalent to 100% and should trigger the fourth state 105 if either thepercent change or absolute change in pulse pressure in conjunction withthe change in diastolic pressure exceeds the prescribed thresholds. Itwill be recognized, however, that other triggering criteria and schemesmay be utilized if desired. Such alternate criteria and schemes may evenbe made specific to individual patient's or groups of patients, basedfor example on historical or anecdotal data or other indicia.

The operation of the exemplary embodiment of the rapid shift detectionalgorithm according to the present invention is now described in detail.As shown in FIG. 4, the algorithm of this embodiment is based upon thewaveform-restored but unscaled beat pressure diastolic and pulsepressure algorithms. The pulse pressure and diastolic beat pressure dataare in this embodiment processed through similar (yet not identical)parallel sub-processes to calculate current and past pressure data foruse in the aforementioned threshold determinations of the third process400. A primary difference between these two sub-processes is that in thefirst sub-process 440, drops in pulse pressure are of most concern,whereas in the second sub-process 442 changes in diastolic pressure areconsidered. Exemplary embodiments of these sub-processes 440, 442 arenow described in greater detail, although it will be appreciated thatother parameters (e.g., besides pulse pressure and diastolic pressure)may be used as the basis for rapid shift detection, and/or otherspecific configurations of these sub-processes may be substituted.

Furthermore, while the exemplary algorithms and functionality aredescribed in terms of first-in-first-out (FIFO) buffers, other bufferingarrangements may be utilized depending on the desired functionality fora given application. For example, under certain circumstances, it may bedesirable to replace portions of data in a LIFO (last-in-first-out)manner. Alternatively, “intelligent” (e.g., algorithmically driven)queuing and de-queuing of data may be incorporated. All such alternateapproaches are readily implemented by those of ordinary skill in thedata processing arts, and accordingly not described further herein.

-   -   i) Pulse Pressure Sub-process (Pre-filtering and Averaging)—The        following pre-filtering and averaging features are employed in        the exemplary embodiment of the first sub-process 440 used in        analyzing pulse pressure:        -   a. Hampel Filter—A Hampel filter (length 7) of the type            previously described is used to remove abhorrent pulse            pressure values from subsequent calculations, as shown in            Eqn. 6 below. Note that a by-product of the exemplary Hampel            Filter is the calculation of variance among the pulse            pressures over the last 7 beats. This information is used            subsequently to determine if the current pulse pressure            should be included in the “acceptable” pulse pressure            circular buffer.            PP _(h)(k)=Hampel Filter{PP(k),PP(k−1),PP(k−2), . . .            PP(k−6)}  (Eqn. 6)            where k represents the current beat number, PP_(h)(k) is the            Hampel filtered pulse pressure, and PP(k) is the current            unfiltered pulse pressure.

Furthermore, the Hampel filter of the present embodiment also calculatesthe variance of the data. The variance is a measure of distributionaround the mean. It is computed as the average squared deviation of eachnumber from its mean, as illustrated in Eqn. 7:PP _(var)(k)=((PP(k)−u)²+(PP(k−1)−u)²+ . . . +((PP(k−6)−u)²)/7,  (Eqn.7)where k represents the current beat number, PP_(var)(k) is the varianceof the pulse pressure over the last 7 beats, and u is the averageunfiltered pulse pressure for the last 7 beats.

-   -   -   b. Pulse Buffer—A pulse buffer (length=8 in the exemplary            embodiment) is a circular buffer containing the            Hampel-filtered pulse pressure values. With each beat, the            oldest beat is replaced with the most recent Hampel-filtered            data.        -   c. Block Averager—A block averaging routine calculates the            mean for the Hampel-filtered pulse pressure data stored in            the aforementioned pulse buffer, as illustrated by Eqn. 8            below.            PP _(h)(k)=[PP _(h)(k)+PP _(h)(k−1)+ . . . +PP _(h)(k−7)]/8              (Eqn. 8)            where PP _(h)(k) is the block averaged Hampel filtered pulse            pressure data.

    -   ii) Pulse Pressure Sub-process (Determining Current Pulse        Pressure)—The following features are utilized in the present        embodiment of the pulse pressure sub-process 440 for determining        the current pulse pressure:        -   a. Maximum—This feature of the algorithm determines the            maximum difference between the current pulse pressure and            the block averaged Hampel-filtered pulse pressure data, as            shown below in Eqn. 9. This maximum is used in subsequent            analysis as the Current Pulse Pressure variable.            If( PP _(h)(k)>PP _(h)(k))PP _(max) [k]=PP _(h)(k)            Else PP _(max) [k]=PP _(h)(k)  (Eqn. 9)            where PP_(max)[k] is used in subsequent comparisons to            detect shifts in mechanical coupling. Note that the trigger            for the fourth state 105 of the first process 100 is, in the            illustrated embodiment, dependant on a significant decrease            in pulse pressure. Thus, under conditions where the average            pulse pressure is small, the system should not trigger if            the pulse pressure from the last beat is large.

    -   iii) Pulse Pressure Sub-process (Determining Past Qualified        Pulse Pressures)—The following features are used in the present        embodiment for determining past (e.g., 12 & 24 beat) qualified        pulse pressure values.        -   a. Variance Buffer—In the exemplary embodiment, a variance            buffer (e.g., length=120) comprises a circular buffer            containing the variance in the pulse pressure for the last            “x” (e.g. 7) beats, as calculated within Hampel filter            operation. With each beat, the data of the oldest beat is            replaced with the most recent variance.        -   b. Block Averager and Standard Deviation—These features            calculate the mean pressure for the variance in the Hampel            filtered pulse pressure data stored in the buffer, as            illustrated in Eqns. 10 and 11 below, respectively. With the            buffer length set at a comparatively large value (e.g.,            120), these calculations provide a statistical benchmark for            typical average and range of variance observed for the            blocks of pulse pressure data. Output of these algorithms is            both block average and standard deviation (or alternatively            an equivalent measure that will enable detection of pulse            pressures that are not within normal limits of the average            mean pressure for the last number of beats n, where n=120 in            the present embodiment).            PP _(var)(k)=[PP _(var)(k)+PP _(var)(k−1)+ . . . +PP            _(var)(k−119)]/120   (Eqn. 10)            where PP _(var)(k) is the block averaged Hampel filtered            pulse pressure data.            SD _(PPvar)(k)=(((PP _(var)(k)− PP _(var)(k))²+(PP            _(var)(k−1)−PP _(var)(k))²+ . . . +((PP _(var)(k−119)− PP            _(var)(k))²)/120)^(1/2)   (Eqn. 11)            where SD_(PPvar)(k) is the standard deviation in the Pulse            Pressure Variance data.        -   c. Stationarity Limit—The stationary limit feature            calculates an upper limit of the pulse pressure variance or            standard deviation that permits the current block (e.g., 7            beats) average pulse pressure to be included in the history            of “qualified” pulse pressure values for future comparisons.            One exemplary approach comprises comparing the variance of            the current pulse pressure block with the value (average            pulse pressure+1 standard deviation of the variances            observed over the last 120 beats), which constitutes the            upper limit of acceptable pulse pressures variance, as shown            in Eqn. 12 below:            StationarityLimit_(pp)(k)= PP _(var)(k)+SD            _(PPvar)(k)  (Eqn. 12)            Note, however, that other methods of determining an upper            limit for the observed variance may readily be substituted            or used in conjunction with the foregoing. For example,            analysis of the current variance (e.g., current            variance<40^(th) largest out of 120 beats) may be utilized.            It will be recognized that the aforementioned median filter            can be easily modified to recursively determine this value.            Other configurations may also be employed consistent with            the invention, such configurations being readily determined            by those of ordinary skill.        -   d. Identification of Pulse Pressure value to be included in            Pulse Pressure History Buffer—The exemplary embodiment of            the invention further includes functionality which            determines whether the current average pulse pressure value            or most recent acceptable pulse pressure value should be            added to the circular buffer containing a history of average            pulse pressures, as shown in Eqn. 13 below. This is            accomplished using the stationarity limit calculated            previously.            If(PP _(var)(k)> PP _(var)(k)+SD _(PPvar)(k))PPhistory            (k)=PPhistory(k−1)            Else PPhistory(k)= PP _(h)(k)  (Eqn. 13)            where PPhistory(k) is the history of “acceptable” Pulse            Pressures        -   e. Update Pulse Pressure History Buffer—In the exemplary            embodiment, a pulse pressure history FIFO buffer (e.g.,            length=24) is employed. The history buffer comprises a            circular buffer containing the history of past “acceptable”            average pulse pressure values. With each beat, the data            associated with oldest beat is replaced with that of the            most recent. Values which are a prescribed number of beats            in the past (e.g., 12 and 24 beats) from this array are used            in subsequent calculations to determine the change in pulse            pressure over this period.

    -   iv) Diastolic Pressure Sub-process (Pre-filtering and        Averaging)—The following pre-filtering and averaging features        are employed in the exemplary embodiment of the first        sub-process 440 used in analyzing pulse pressure:        -   a. Hampel Filter—The exemplary embodiment of the diastolic            sub-process 442 uses a Hampel filter (e.g., length 7) to            remove abhorrent diastolic pressure values from subsequent            calculations, similar to the pulse pressure sub-process 440            (see Eqn. 14 below). A by-product of the Hampel Filter is            the calculation of the variance of diastolic pressure over            the previous number (e.g., 7) of beats. This information is            used subsequently to determine if the current diastolic            pressure should be included in the “acceptable” diastolic            pressure circular buffer.            D _(h)(k)=Hampel Filter{D(k), D(k−1), D(k−2), . . .            ,D(k−6)}  (Eqn. 14)            where k represents the current beat number, D_(h)(k) is the            Hampel filtered diastolic pressure, and D(k) is the current            unfiltered diastolic pressure. Furthermore, the Hampel            filter also calculates the variance of the data, as shown in            Eqn. 15:            D _(var)(k)=((D(k)−u)²+(D(k−1)−u)²+ . . . +            ((D(k−6)−u)²)/7,  (Eqn. 15)            where k represents the current beat number, D_(var)(k) is            the variance of the diastolic pressure over the last 7            beats, and u is the average diastolic pressure over the last            7 beats.        -   b. Pulse Buffer—A FIFO pulse buffer of a determinate length            (e.g., length=8) is used in the present embodiment; this            buffer comprises a circular buffer containing the Hampel            filtered diastolic pressure values. With each successive            beat, the data for the oldest beat is replaced with the most            recent Hampel filtered data.        -   c. Block Averager—A block averaging routine is used to            calculate the mean for the Hampel filtered diastolic            pressure data stored in the buffer, as shown in Eqn. 16            below:            D _(h)(k)=[D _(h)(k)+D _(h)(k−1)+ . . . +D _(h)(k−7)]/8              (Eqn. 16)            where D _(h)(k) is the block averaged Hampel filtered            Diastolic pressure data.

    -   v) Diastolic Pressure Sub-process (Current Value        Determination)—The diastolic sub-process 442 determines the        current value of the diastolic pressure using a straightforward        methodology. Specifically, the current diastolic pressure is        simply the most recent block averaged Hamper-filtered diastolic        pressure value. Note that the trigger for the fourth state 105        of the first process 100 is dependant on a significant change in        diastolic pressure.

    -   vi) Diastolic Pressure Sub-process (Determining Past Qualified        DiastolicPressures)—The sub-process 442 also contains mechanisms        for determining past qualified diastolic pressures (e.g., those        of 12 and 24 beats past), as follows:        -   a. Variance Buffer—A FIFO variance buffer of determinate            length (e.g., length=120) comprising a circular buffer            containing the variance in the diastolic pressure for the            last 7 beats (as calculated within Hampel filter operation)            is used in the present embodiment of the diastolic            sub-process 442. With each beat, the variance of the oldest            beat is replaced with the most recent variance.        -   b. Block Averager and Standard Deviation—These functions            calculate the mean for the variance in the Hampel-filtered            diastolic pressure data stored in the variance buffer. With            the buffer length set at a comparatively large value, these            calculations provide a statistical benchmark for the typical            average and the range of variance observed for the blocks of            pulse pressure. Output from these processes is both block            average and standard deviation (or an equivalent measure)            that will enable detection of pulse pressures that are not            within normal limits of the average mean pressure for the            last “n” beats), as shown in Eqns. 17 and 18 below (for            n=120):            D _(var)(k)=[D _(var)(k)+D _(var)(k−1)+ . . . +D            _(var)(k−119)]/120  (Eqn. 17)            SD _(Dvar)(k)=(((D _(var)(k)− D _(var)(k))²+(D _(var)(k−1)−            D _(var)(k))² + . . . +((D _(var)(k−119)− D            _(var)(k))²)/119)^(1/2)   (Eqn. 18)            where D _(var)(k) is the block averaged Hampel filtered            diastolic pressure data.        -   c. Stationarity Limit—The stationary limit function of the            diastolic sub-process 442 calculates an upper limit of the            diastolic pressure variance (or standard deviation) that            permits the average diastolic pressure of the current block            of data (e.g., 7 beats-worth) to be included in the history            of diastolic pressure values for use in future comparisons,            as shown in Eqn. 19:            StationarityLimit_(D)(k)= D _(var)(k)+/−SD _(Dvar)(k)  (Eqn.            19)        -   d. Identify Diastolic Pressure value to be included in            Diastolic Pressure History Buffer—Using the stationarity            limit previously calculated, this feature of the diastolic            sub-process 442 determines whether the current average            diastolic pressure value or most recent “acceptable”            diastolic pressure value should be added to the circular            buffer containing a history of average pulse pressures. If            the new Diastolic Pressure is within limits of the            stationarity limit described above, then it is included in            the diastolic pressure history, else the most recent            diastolic pressure history value is duplicated.        -   e. Update Diastolic Pressure History Buffer—In the exemplary            embodiment, the diastolic subprocess 442 includes a circular            FIFO buffer of determinate length (e.g., length=24)            containing the history of past “acceptable” average            diastolic pressures. With each beat, the data associated            with the oldest beat is replaced with that of the most            recent. Values derived from one or more past beats (e.g., 12            and 24 beats in the past from the current array) are used in            subsequent calculations to determine the change in pulse            pressure over the period of interest, as shown in Eqn. 20            below:            If(D _(var)(k)> D _(var)(k)+SD            _(Dvar)(k))Dhistory(k)=Dhistory(k−1)            Else Dhistory(k)=⁻ D _(h)(k)  (Eqn. 20)

    -   vii) Analysis for Detection of Shifts in Mechanical Coupling        -   a. Threshold detection—In order to detect rapid shifts in            mechanical coupling, the third process 400 of the invention            performs threshold detection over the prior first number            (e.g., 12) of beats in the exemplary embodiment as follows:        -   1) Pulse Pressure Difference—The third process 400            calculates the difference between the current pulse pressure            (Current Pulse Pressure variable referenced with respect to            Item ii.a. of the pulse pressure sub-process 440 above) and            the first number (e.g., 12) of qualified pulse pressure            beats in the past (stored in the circular history buffer by            the pulse pressure sub-process 440 as previously described            in iii.d. above). This calculation is shown in Eqn. 21            below:            PulsePressureDifference12=PP _(max) [k]−PPhistory(12)  (Eqn.            21)

    -   2) Diastolic Difference—The third process 400 calculates the        difference between the current diastolic pressure (output from        the diastolic sub-process block averager as described above) and        the qualified diastolic pressure for, e.g., 12 beats in the past        (stored in the circular history buffer by the diastolic        sub-process as described in Item vi.d. above), as shown in Eqn.        22:        DiastolicPressureDifferencel2= D _(h)(k)−Dhistory(12)  (Eqn. 22)

    -   3) Detector—In accordance with the temporal threshold shown in        FIG. 4 a, if the pulse pressure difference (Item vii.a.1) above)        is sufficiently negative, and the diastolic pressure difference        (Item vii.a.2) above) is sufficiently different from zero, then        a “Trigger 1” value 448 associated with the fourth state 105 of        the first process 100 is set to TRUE.        -   b. Additionally, the third process 400 of the invention            performs threshold detection over the prior second number            (e.g., 24) of beats in the exemplary embodiment as follows:

    -   1) Pulse Pressure Difference—The third process 400 calculates        the difference between the current pulse pressure (Current Pulse        Pressure variable referenced above) and the qualified second        number (e.g., 24) of pulse pressure beats in the past (stored in        the circular history buffer by the pulse pressure sub-process        440 as previously described), as shown in Eqn 23 below:        PulsePressureDifference24=PP _(max) [k]−PPhistory(24)  (Eqn. 23)

    -   2) Diastolic Difference: Calculates the difference between the        current diastolic pressure (as previously described) and the        qualified diastolic pressure 24 beats in the past, as        illustrated by Eqn. 24 below:        DiastolicPressureDifference24= D _(h)(k)−Dhistory(24)  (Eqn. 24)

    -   3) Detector—In accordance with the temporal (e.g., 24 second)        threshold shown in FIG. 4 a, i the pulse pressure difference        (Item vii.b.1) above) is sufficiently negative, and the        diastolic pressure difference (Item viii.b.2) above) is        sufficiently different from zero, then the “Trigger 2” value 450        for the fourth state 105 of the second process is set TRUE.        -   c. Beat Evaluation over Most Recent Period—Additionally, the            third process 400 of the present invention is optionally            configured to evaluate beats detected within a prior            interval (e.g., prior five seconds), as follows:

    -   1) No beat detected during interval—If a beat of acceptable        quality has not been detected over the interval and “noise” on        the pressure signal has not caused the lack of a good beat, then        the “Trigger 3” value 452 for the fourth state 105 is set TRUE.        -   d. Fourth State Request Check—The third process 400 performs            a logic check based on the presence of a Trigger 1, Trigger            2, or Trigger 3 value 448, 450, 452 set to TRUE. If any of            the aforementioned Triggers are set TRUE, and the first            process 100 is in the first state 102, then the first            process 100 should enter the fourth state 105 (i.e.,            accelerated recovery). All fourth state Triggers 448, 450,            452 are then reset to FALSE.

Note that if the first process 100 is in either the second state 103 orthird state 104, the proper new state option is subsequently determined.Alternatively, if the first process is currently in the fourth state105, then the aforementioned request to enter the fourth state 105 isignored.

It will be recognized that while the foregoing embodiment of the thirdprocess methodology addresses the problem of identifying rapid shifts inmechanical coupling based on a substantially probabilistic approach(which is tailored using an understanding of common changes in apatient's arterial pressure during the course of various physiologicevents), this approach does not measure directly (or even indirectly)changes in the mechanical coupling between the tonometric pressuresensor and its associated contact pad and the underlying tissue.Accordingly, the exemplary implementation of the third process 400 isnot immune to error. The second process 200 of the present invention,however, advantageously insulates the system against failure of thethird process 400 to detect rapid changes in coupling, since the secondprocess will converge on the optimal level of applanation irrespectiveof the third process (albeit over a period of several minutes) aspreviously described. Furthermore, false triggering by the third process400 (i.e., indication that a rapid coupling change has been experiencedwhen in fact it has not) will induce an applanation sweep, and possiblya lateral/proximal position sweep, which enables the system to recoveras well. Hence, any errors associated with the probabilisticimplementation of the third process 400 do not adversely affect theaccuracy of the system, but rather merely the speed with which itconverges on the proper applanation level and/or lateral or proximalposition. The exemplary embodiment of the present invention willtherefore not generate “bad” data, but rather simply not update datauntil optimal applanation/position is achieved.

It will also be noted that examination of a patient's data history asdescribed above with respect to the pulse pressure and diastolicsub-processes 440, 442 may encompass examinations of selected segmentsof the data history for that patient as well as the examination andcomparison of segments of data for that patient against comparable datafor other patients. Furthermore, the analysis described above may beapplied in both historical and/or predictive fashion; for instance, oneor more historical data segments may be analyzed via an algorithm whichpredicts future ranges or values for one or more parameters. If thesubsequent measurement of the parameter(s) is not within the prediction,instigation of the applanation/position sweep(s) can then conducted andthe optimal position reacquired. For example, wherein an analysis of thehistorical data for a patient relating to diastolic pressure indicatesthat a future measurement within a given time epoch τ outside the rangeof 50–80 mmHg would correspond to an unphysical situation or event, anydiastolic pressure reading outside that range occurring within τ couldtrigger reacquisition.

It will further be recognized that numerous combinations of analyzedparameters (e.g., systolic, diastolic, pulse, or mean pressure, andcombinations or derivations thereof), time periods (historical,historical/predictive, or purely predictive), and acceptance/rejectioncriteria (e.g., parameter range at a discrete epoch, continuity orvariation over time, statistics, etc.) may be utilized either alone orin combination consistent with the present invention to effectuate thegoal of maintaining optimal position of the sensor under all operatingenvironments and conditions. All such methods and approaches are readilyimplemented within the framework of the present invention by those ofordinary skill in the programming and mathematical arts, and accordinglyare not described further herein.

System Apparatus for Hemodynamic Assessment

Referring now to FIG. 5, an apparatus for measuring hemodynamicproperties within the blood vessel of a living subject is now described.In the illustrated embodiment, the apparatus is adapted for themeasurement of blood pressure within the radial artery of a human being,although it will be recognized that other hemodynamic parameters,monitoring sites, and even types of living organism may be utilized inconjunction with the invention in its broadest sense.

The exemplary apparatus 500 of FIG. 5 fundamentally comprises anapplanation assembly (including one or more pressure transducers 522)for measuring blood pressure from the radial artery tonometrically; adigital processor 508 operatively connected to the pressuretransducer(s) 522 (and a number of intermediary components) for (i)analyzing the signals generated by the transducer(s); (ii) generatingcontrol signals for the stepper motor 506 (via a microcontroller 511 aoperatively coupled to the stepper motor control circuits); and (iii)storing measured and analyzed data. The motor controllers 511, processor508, auxiliary board 523, and other components may be housed eitherlocally to the applanator 502, or alternatively in a separatestand-alone housing configuration if desired. The pressure transducer522 and its associated storage device 552 are optionally made removablefrom the applanator 502.

The pressure transducer 522 is, in the present embodiment, a strain beamtransducer element which generates an electrical signal in functionalrelationship (e.g., proportional) to the pressure applied to its sensingsurface 521, although other technologies may be used. The analogpressure signals generated by the pressure transducer 522 are convertedinto a digital form (using, e.g., an ADC 509) after being optionallylow-pass filtered 513 and sent to the signal processor 508 for analysis.Depending on the type of analysis employed, the signal processor 508utilizes its program either embedded or stored in an external storagedevice to analyze the pressure signals and other related data (e.g.,stepper motor position as determined by the position encoder 577,scaling data contained in the transducer's EEPROM 552 via I2C1 signal,need for reacquisition per FIG. 4, etc.).

As shown in FIG. 5, the apparatus 500 is also optionally equipped with asecond stepper motor 545 and associated controller 511 b, the secondmotor 545 being adapted to move the applanator assembly 502 laterallyacross the blood vessel (e.g., radial artery) of the subject asdescribed above. A third stepper motor (not shown) and associatedcontrols may also be implemented if desired to control the proximalpositioning of the applanation element 502. Operation of the lateralpositioning motor 545 and its controller 511 b is substantiallyanalogous to that of the applanation motor 506, consistent with themethodologies previously described herein.

As previously discussed, continuous accurate non-invasive measurementsof hemodynamic parameters (e.g., blood pressure) are highly desirable.To this end, the apparatus 500 is designed to (i) identify the properlevel of applanation of the subject blood vessel and associated tissue;(ii) continuously “servo” on this condition to maintain the bloodvessel/tissue properly biased for the best possible tonometricmeasurement; optionally (iii) scale the tonometric measurement as neededto provide an accurate representation of intravascular pressure to theuser/operator; and (iv) identify conditions where transient or“unphysical” events have occurred, and correct the system accordingly toregain the optimal applanation level and lateral/proximal positions.

During an applantion “sweep”, the controller 511 a controls theapplanation motor 506 to applanate the artery (and interposed tissue)according to a predetermined profile. Similarly, the extension andretraction of the applanation element 502 during the later states of thealgorithm (i.e., when the applanation motor 506 is disposed at theoptimal applanation position, and subsequent servoing around this point)are controlled using the controller 511 a and processor 508. Such“servo” control schemes may also be employed with respect to the lateraland proximal motor drive assemblies if desired, or alternatively a morestatic approach (i.e., position to an optimal initial position, and thenreposition only upon the occurrence of an event causing significantmisalignment). In this regard, it will be recognized that the controlschemes for the applanation motor and the lateral/proximal positioningmotor(s) may be coupled to any degree desired consistent with theinvention.

The apparatus 500 is also configured to apply the methodologies of thefirst, second, and third processes 100, 200, 400 previously discussedwith respect to FIGS. 1–4, as well as the initial sweep and scalingmethodologies described in the aforementioned co-pending patentapplication Ser. No. 10/072,508 previously incorporated by referenceherein. Details of the implementation of these latter methodologies areprovided in the co-pending application, and accordingly are notdescribed further herein.

The physical apparatus 500 of FIG. 5 comprises, in the illustratedembodiment, a substantially self-contained unit having, inter alia, acombined pressure transducer 522 and applanation device 500, motorcontrollers 511, RISC digital processor 508 with associated synchronousDRAM (SDRAM) memory 517 and instruction set (including scaling lookuptables), display LEDs 519, front panel input device 521, and powersupply 523. In this embodiment, the controllers 511 is used to controlthe operation of the combined pressure transducer/applanation device,with the control and scaling algorithms are implemented on a continuingbasis, based on initial operator/user inputs.

For example, in one embodiment, the user input interface comprises aplurality (e.g., two) buttons disposed on the face of the apparatushousing (not shown) and coupled to the LCD display 579. The processorprogramming and LCD driver are configured to display interactive promptsvia the display 579 to the user upon depression of each of the twobuttons.

Furthermore, a patient monitor (PM) interface circuit 591 shown in FIG.5 may be used to interface the apparatus 500 to an external orthird-party patient monitoring system. Exemplary configurations for suchinterfaces 591 are described in detail in co-pending U.S. patentapplication Ser. No. 10/060,646 entitled “Apparatus and Method forInterfacing Time-Variant Signals” filed Jan. 30, 2002, and assigned tothe Assignee hereof, which is incorporated by reference herein in itsentirety, although other approaches and circuits may be used. Thereferenced interface circuit has the distinct advantage of automaticallyinterfacing with literally any type of patient monitor system regardlessof its configuration. In this fashion, the apparatus 500 of the presentinvention coupled to the aforementioned interface circuit allowsclinicians and other health care professionals to plug the apparatusinto in situ monitoring equipment already on hand at their facility,thereby obviating the need (and cost) associated with a dedicatedmonitoring system just for blood pressure measurement.

Additionally, an EEPROM 552 is physically coupled to the pressuretransducer 522 as shown in FIG. 5 so as to form a unitary unit which isremovable from the host apparatus 500. The details of the constructionand operation of exemplary embodiments of such coupled assemblies aredescribed in detail in co-pending U.S. application Ser. No. 09/652,626,entitled “Smart Physiologic Parameter Sensor and Method”, filed Aug. 31,2000, assigned to the Assignee hereof, and incorporated by referenceherein in its entirety, although other configurations clearly may besubstituted. By using such a coupled and removable arrangement, both thetransducer 522 and EEPROM 552 may be readily removed and replaced withinthe system 500 by the operator.

It is also noted that the apparatus 500 described herein may beconstructed in a variety of different configurations, and using avariety of different components other than those specifically describedherein. For example, it will be recognized that while many of theforegoing components such as the processor 508, ADC 509, controller 511,and memory are described effectively as discrete integrated circuitcomponents, these components and their functionality may be combinedinto one or more devices of higher integration level (e.g., so-called“system-on-chip” (SoC) devices). The construction and operation of suchdifferent apparatus configurations (given the disclosure providedherein) are readily within the possession of those of ordinary skill inthe medical instrumentation and electronics field, and accordingly notdescribed further herein.

The computer program(s) for implementing the aforementioned first,second, and third processes (as well as scaling) are also included inthe apparatus 500. In one exemplary embodiment, the computer programcomprises an object (“machine”) code representation of a C⁺⁺ source codelisting implementing the methodology of FIGS. 1–4, either individuallyor in combination thereof. While C⁺⁺language is used for the presentembodiment, it will be appreciated that other programming languages maybe used, including for example VisualBasic™, Fortran, and C⁺. The objectcode representation of the source code listing is compiled and may bedisposed on a media storage device of the type well known in thecomputer arts. Such media storage devices can include, withoutlimitation, optical discs, CD ROMs, magnetic floppy disks or “hard”drives, tape drives, or even magnetic bubble memory. These programs mayalso be embedded within the program memory of an embedded device ifdesired. The computer program may further comprise a graphical userinterface (GUI) of the type well known in the programming arts, which isoperatively coupled to the display and input device of the host computeror apparatus on which the program is run.

In terms of general structure, the program is comprised of a series ofsubroutines or algorithms for implementing the applanation and scalingmethodologies described herein based on measured parametric dataprovided to the host apparatus 500. Specifically, the computer programcomprises an assembly language/micro-coded instruction set disposedwithin the embedded storage device, i.e. program memory, of the digitalprocessor or microprocessor associated with the hemodynamic measurementapparatus 500. This latter embodiment provides the advantage ofcompactness in that it obviates the need for a stand-alone PC or similarhardware to implement the program's functionality. Such compactness ishighly desirable in the clinical and home settings, where space (andease of operation) are at a premium.

Method of Providing Treatment

Referring now to FIG. 6, a method of providing treatment to a subjectusing the aforementioned methods is disclosed. As illustrated in FIG. 6,the first step 602 of the method 600 comprises selecting the bloodvessel and location to be monitored. For most human subjects, this willcomprise the radial artery (as monitored on the inner portion of thewrist), although other locations may be used in cases where the radialartery is compromised or otherwise not available.

Next, in step 604, the applanation mechanism 502 is placed in the properlocation with respect to the subject's blood vessel. Such placement maybe accomplished manually, i.e., by the caregiver or subject by visuallyaligning the transducer and device over the interior portion of thewrist, by the pressure/electronic/acoustic methods of positioningpreviously referenced, or by other means. Next, the first applanationelement 502 is operated per step 606 so as to applanate the tissuesurrounding the blood vessel to a desired level so as to identify anoptimal position where the effects of transfer loss and other errorsassociated with the tonometric measurement are mitigated. Co-pending U.Spatent application Ser. No. 10/072,508 previously incorporated hereinillustrates one exemplary method of finding this optimum applanationlevel.

Once the optimal level of applanation for the applanator element 502 isset, the pressure waveform is measured per step 608, and the relevantdata processed and stored as required (step 610). Such processing mayinclude, for example, calculation of the pulse pressure (systolic minusdiastolic), calculation of mean pressures or mean values over finitetime intervals, and optional scaling of the measured pressurewaveform(s). One or more resulting outputs (e.g., systolic and diastolicpressures, pulse pressure, mean pressure, etc.) are then generated instep 612 based on the analyses performed in step 610. The relevantportions of the first, second, and third processes 100, 200, 400 of thepresent invention are then implemented as required to maintain thesubject blood vessel and overlying tissue in a continuing state ofoptimal or near-optimal compression (as well as maintaining optimallateral/proximal position if desired) per step 614 so as to providecontinuous monitoring and evaluation of the subject's blood pressure.This is to be distinguished from the prior art techniques and apparatus,wherein only periodic representations and measurement of intra-arterialpressure are provided.

Lastly, in step 616, the “corrected” continuous measurement of thehemodynamic parameter (e.g., systolic and/or diastolic blood pressure)is used as the basis for providing treatment to the subject. Forexample, the corrected systolic and diastolic blood pressure values arecontinuously generated and displayed or otherwise provided to the healthcare provider in real time, such as during surgery. Alternatively, suchmeasurements may be collected over an extended period of time andanalyzed for long term trends in the condition or response of thecirculatory system of the subject. Pharmacological agents or othercourses of treatment may be prescribed based on the resulting bloodpressure measurements, as is well known in the medical arts. Similarly,in that the present invention provides for continuous blood pressuremeasurement, the effects of such pharmacological agents on the subject'sphysiology can be monitored in real time.

It is noted that many variations of the methods described above may beutilized consistent with the present invention. Specifically, certainsteps are optional and may be performed or deleted as desired.Similarly, other steps (such as additional data sampling, processing,filtration, calibration, or mathematical analysis for example) may beadded to the foregoing embodiments. Additionally, the order ofperformance of certain steps may be permuted, or performed in parallel(or series) if desired. Hence, the foregoing embodiments are merelyillustrative of the broader methods of the invention disclosed herein.

While the above detailed description has shown, described, and pointedout novel features of the invention as applied to various embodiments,it will be understood that various omissions, substitutions, and changesin the form and details of the device or process illustrated may be madeby those skilled in the art without departing from the spirit of theinvention. The foregoing description is of the best mode presentlycontemplated of carrying out the invention. This description is in noway meant to be limiting, but rather should be taken as illustrative ofthe general principles of the invention. The scope of the inventionshould be determined with reference to the claims.

1. A method of transient event compensation during hemodynamic parametermeasurement from a compressible blood vessel, comprising: establishingan initial substantially optimal level of compression of said bloodvessel for at least a first epoch; measuring pressure data from saidblood vessel using a sensor; detecting the occurrence of a transientevent by analyzing changes in said pressure data, said transient eventaltering the mechanical coupling between said blood vessel and sensor;initiating a pressure sweep to identify a second substantially optimallevel of compression based on said altered coupling; and establishingthe second substantially optimal level of compression of said bloodvessel for at least a second epoch.
 2. The method of claim 1, furthercomprising waiting for said transient event to subside before initiatingsaid sweep.
 3. The method of claim 1, wherein said act of initiating apressure sweep comprises: analyzing pressure data relating to at leasttwo time periods occurring before and after said transient event,respectively; comparing changes in said pressure data from said at leasttwo time periods to a criterion; and initiating said pressure sweep whensaid criterion is satisfied.
 4. A method of operating a continuousnon-invasive blood pressure measurement system adapted for use on theradial artery of a living subject and having a tonometric pressuresensor in contact with the tissue overlying said artery, comprising:operating said system in a non-transient mode, wherein blood pressuredata is obtained using said sensor; detecting at least one transientevent using said blood pressure data; and operating said system in atransient recovery mode subsequent to said detection of said event. 5.The method of claim 4, wherein said non-transient mode comprises a modewherein a level of compression applied to said artery is varied in orderto maintain said artery in a substantially optimal state of compressionfor said act of obtaining blood pressure data.
 6. The method of claim 5,wherein said transient recovery mode comprises performing a sweep acrossa plurality of levels of said compression of said artery in order toreacquire said substantially optimal state.
 7. The method of claim 5,wherein said compression of said artery is applied using said sensor. 8.A method of operating a non-invasive blood pressure measurement systemadapted for use on the radial artery of a living subject and having atonometric pressure sensor in contact with the tissue at least partlyoverlying said artery, comprising: operating said system in anon-transient mode, wherein blood pressure data is obtained using saidsensor; detecting at least one transient event during said act ofobtaining said blood pressure data; operating, for at least a period oftime, said system in a transient recovery mode subsequent to saiddetection of said event; and subsequently returning to operating in saidnon-transient mode.
 9. A method of operating a non-invasive hemodynamicmeasurement system, comprising: operating said system in a first mode,wherein hemodynamic data is obtained; detecting at least one transientevent within said hemodynamic data; and (i) operating said system in asecond mode subsequent to said detection of said event if said eventdoes not have a first characteristic; and (ii) operating said system ina third mode subsequent to said detection if said event has said firstcharacteristic; wherein said first characteristic comprises parametersindicating that said event is not (a) physiologic in origin, and (b) ofsufficient magnitude that recovery from said event in said second modewould exceed a first criterion.
 10. The method of claim 9, wherein saidhemodynamic data comprises pressure data, and said act of obtaining saiddata comprises using a non-invasive pressure sensor to obtain said data.11. The method of claim 9, wherein said second mode comprises a modeadapted to selectively vary a level of compression applied via saidpressure sensor.
 12. The method of claim 9, wherein said transient eventcomprises a motion initiated by a subject from which said hemodynamicdata is being obtained, and said act of detecting comprises identifyingat least one artifact within a waveform related to said hemodynamicdata.
 13. The method of claim 12, wherein said act of identifying atleast one artifact within a waveform related to said hemodynamic datacomprises detecting changes in a pressure waveform where diastolicpressure increases and pulse pressure decreases significantly over agiven time period.
 14. The method of claim 12, wherein said act ofidentifying at least one artifact within a waveform related to saidhemodynamic data comprises detecting changes in a first averagedpressure value with respect to a second averaged pressure value.
 15. Themethod of claim 14, wherein said second average pressure value comprisesa value obtained from a moving cardiac beat window.
 16. The method ofclaim 9, wherein said first criterions comprises a maximum time value.17. A method of operating a non-invasive and continuous blood pressuremeasurement apparatus, comprising: operating said apparatus in a firstmode, wherein blood pressure data is obtained from the circulatorysystem of a living subject; detecting at least one transient event basedon said blood pressure data; and operating said system in a second modesubsequent to said detection of said event if said event is determinednot to be of sufficient severity that recovery from said event in saidsecond mode would exceed a first criterion; or operating said system ina third mode subsequent to said detection if said event is determined tobe of sufficient severity that recovery from said event in said secondmode would exceed said first criterion.
 18. The method of claim 17,wherein said act of operating in a second mode further comprisesoperating in said second mode only if said event is determined tooriginate from said circulatory system of said living subject.
 19. Themethod of claim 17, wherein said act of operating in a third modefurther comprises operating in said third mode only if said event isdetermined not to originate from said circulatory system of said livingsubject.
 20. The method of claim 17, wherein said first criterioncomprises a time period or duration.
 21. The method of claim 17, whereinsaid event comprises a movement of at least a portion of said apparatusrelative to said subject.
 22. The method of claim 17, wherein said eventcomprises a movement of at least a portion of said apparatus and saidsubject.
 23. A method of operating a pressure determining apparatusunder transient conditions, comprising: determining a firstsubstantially optimal initial level of compression of a compressiblevessel from which said pressure is measured; operating said apparatus atsaid first substantially optimal level of compression for at least afirst epoch; detecting the occurrence of a transient event; determininga second substantially optimal level of compression of said vessel, saidsecond level being different from said first level, said differenceresulting at least in part from said transient event; and operating saidapparatus at said second substantially optimal level of compression forat least a second epoch, said first and second epochs occurring atdifferent times.
 24. A method of claim 23, wherein said vessel comprisesa blood vessel within the circulatory system of a living subject.
 25. Amethod of claim 23, wherein said vessel comprises a pressure-containingvessel not within the circulatory system of a living subject.
 26. Amethod of operating a non-invasive pressure monitoring apparatus underchanging conditions, comprising: determining a first substantiallyoptimal initial level of compression of a blood vessel from which saidpressure is measured; operating said apparatus at said firstsubstantially optimal level of compression for at least a first epoch;detecting the occurrence of at least one sudden event; determining asecond substantially optimal level of compression of said blood vessel,said second level being different from said first level, said differenceresulting at least in part from said at least one sudden event; andoperating said apparatus at said second substantially optimal level ofcompression for at least a second epoch, said first and second epochsoccurring at different times.
 27. The method of claim 26, wherein saidact of detecting the occurrence of at least one sudden event comprisesdetecting an externally-induced transient.
 28. The method of claim 26,wherein said act of detecting the occurrence of at least one suddenevent comprises detecting a significant change in the coupling between asensor associated with said apparatus used for monitoring said pressureand said blood vessel.
 29. The method of claim 26, wherein said act ofdetermining a second substantially optimal level comprises varying thelevel of compression of said blood vessel over time, and evaluatingblood pressure data obtained during said act of varying.
 30. A method ofoperating a non-invasive blood pressure measurement system adapted foruse on a blood vessel of a living subject and having a means for sensingpressure in contact with the tissue at least partly overlying saidvessel, comprising: a step for operating said system in a non-transientmode, wherein blood pressure data is obtained using said means forsensing; a step for detecting at least one transient event during saidact of obtaining said blood pressure data; and a step for operating, forat least a period of time, said system in a transient recovery modesubsequent to said detection of said event.
 31. A method of operating ameans for determining pressure under transient conditions, comprising: astep for determining a first substantially optimal initial level ofcompression of a compressible vessel from which said pressure ismeasured; a step for operating said means at said first substantiallyoptimal level of compression for at least a first epoch; a step fordetecting the occurrence of a transient event; a step for determining asecond substantially optimal level of compression of said vessel, saidsecond level being different from said first level, said differenceresulting at least in part from said transient event; and a step foroperating said apparatus at said second substantially optimal level ofcompression for at least a second epoch, said first and second epochsoccurring at different times.
 32. A method of operating a non-invasivehemodynamic measurement system, comprising: operating said system in aservo mode, wherein hemodynamic data is obtained; detecting at least onetransient event within said hemodynamic data; and operating said systemin a transient recovery mode subsequent to said detection of said event,said transient recovery mode being adapted to promptly return saidsystem to said servo mode.
 33. The method of claim 32, wherein said actof obtaining hemodynamic data comprises obtaining said hemodynamic datafrom a blood vessel, and said transient recovery mode comprises at leastthe act of performing an applanation sweep of said blood vessel.
 34. Amethod of operating a non-invasive hemodynamic measurement system,comprising: operating said system in a non-transient mode, whereinhemodynamic data is obtained; detecting at least one transient eventwithin said hemodynamic data; and operating said system in a transientrecovery mode subsequent to said detection of said event; wherein saidnon-transient mode comprises modulating compression applied to a bloodvessel from which said hemodynamic data is maintained.
 35. The method ofclaim 34, wherein said modulating compression comprises modulatingaccording to a substantially randomized sequence.
 36. The method ofclaim 35, wherein said act of obtaining hemodynamic data comprisesobtaining said hemodynamic data from a blood vessel, and said transientrecovery mode comprises at least the act of performing an applanationsweep of said blood vessel.
 37. A method of operating a non-invasivehemodynamic measurement system, comprising: operating said system in anon-transient mode, wherein hemodynamic data is obtained; detecting atleast one transient event within said hemodynamic data; operating saidsystem in a transient recovery mode subsequent to said detection of saidevent; and operating in a second non-transient mode when non-transientinduced changes occur, said non-transient changes being detected atleast in part by modulating a compression level of a blood vessel fromwhich said hemodynamic data is obtained.
 38. A method of operating anon-invasive blood pressure measurement apparatus comprising: collectingpressure data in a non-transient mode; detecting the occurrence of atleast one transient event based at least in part on said data; operatingsaid apparatus in a transient recovery mode subsequent to said detectionof said event; and operating in a second non-transient mode whennon-transient induced changes occur, said non-transient changes beingdetected at least in part by modulating a compression level of a bloodvessel from which said data is obtained.